General Anaesthesia

Question 1

Definitions

Answer 1

Anaesthesia- loss of feeling

General anaesthesia: whole body

Local anaesthetic: affects part to which applied

GA: state of reversible unconsciousness with reduced sensitivity (i.e. muscle relaxation and analgesia) and response to stimuli

Three components: unconsciousness, analgesia, muscle relaxation

Balanced anaesthesia combines drugs to optimize these three components, allowing for a more unified state of anaesthesia and lower doses of individual drugs

Question 2

Stages of anaesthesia

Answer 2

with increasing depression of CNS function:

Stage 1: voluntary movement- still aware, conscious; likely to see paddling

Stage 2: involuntary movement or excitement- lost consciousness, but limbs may still be working

Stage 3: surgical anaesthesia- not responsive and fully unconcious

Stage 4: medullary paralysis- depress brain function that controls CV/resp function–> detrimental effects

Question 3

Why do we anaesthetize animals?

Answer 3

to perform painful surgical or diagnostic procedures

Aims: to minimize patient suffering, reduce risk to vet, facilitate the proceudre by immoblizing the patient (i.e. CT/MRI)

Question 4

Combo of drugs to achieve anaesthesia

Answer 4

Premedicants: drugs given prior to a GA; typically a sedative-opioid combo

Induction drugs: typically IV- drugs used to achieve tranisition from consciousness to unconsciousness

Maintenance drugs: drugs used to maintain anaesthetic state (can be same drug used for induction or two different drugs)

Question 5

Lipid theory of anaesthesia

Answer 5

drugs partition into the lipid bilayer of cell and by dissolving drugs, change fluidity–> change dimensions/permeability of the membrane

Pros: 1) correlation: lipid solubility and potency have direct correlation 2) pressure reversal: by increasing hydrostatic pressure, anaesthesia was reversed. Also increase excitability–>restore normal function

Cons: 1) temperature: temp change can cause similar fluidity changes in membrane, but doesn’t cause anaesthesia 2) stereoselectivity: both isomers exactly the same lipid solubility but one elicits anaesthesia and the other doesn’t 3) cut-off phenomenon: GA molecules are hydrocarbon chains. up to a point, if you increase chain legnth, you increase the potentcy, but at some point, you lose potency, even as lipid solubility continues to increase with increasing chain length. 4) correlation with enzyme inhibition

bottom line: lipid solubility likely has moreto do with GETTING to the target

Question 6

Protein theory of anaesthesia

Answer 6

GAs work by interacting with a protein

Receptor interaction: i.e. thiopentone with GABA receptors

Small hyperpolarisaion with 3mmol of GABA. 3mmol in the presence of propofol results in MUCH larger hyperopolarization. see similar effects with Etomidate. Genetically modified cell with change in GABA receptor–> takes away effect of propofol and etomidate.

Two pore domain K channels: relatively new target–> regulators of membrane excitability of CNS. if you have modified channels, does response curve shifted to the right and get less sensititivy to halothane.

Likely, GAs work by interacting/target with more than one receptor, i.e. glycine receptors, NMDA receptors, Na+ channels

Question 7

Effects of GA on CVS and Respiration

Answer 7

decrease contractility of isolated heart preparations

effects on CO and BP vary

cardiac dysrrhytmia- halothane particularly sensitizes heart to catecholamines

decreased respiration (bear in mind when using with opiates)

increase arterial pCO2

Question 8

Effects of GA on nervous system

Answer 8

@ cellular level: inhibit conduction of APs

inhibit transmission at synapses- 1) decrease NT release 2) decrease action of NT 3) decrease excitability of post-synaptic cell

Reticular formation (responsible for cortical arousal) and hippocampus (responsible for short term memory) are particularly susceptible

Question 9

IV anaesthetic agents

Answer 9

typically used to induce anaesthesia- occasionally used to maintain anaesthesia (see TIVA)

Advantages: 1) rapid smooth induction 2) rapid protection of the airway- for maintainence of patent, protected airway (also for inhalational agents)- important in dyspneic patients and those at risk of regurg/aspiration 3) no environmental pollution

Disadvantages: IV access required- small patients or patients with thrombosed veins

Question 10

Ideal properties of IV anaesthetic

Answer 10

stable on storage

non-irritant to veins or perivascular tissues

rapid/smooth induction

rapid metabolism- no accumulation

rapid/smooth emergency and recovery

non-toxic to liver/kidneys

minimal adverse CVS or resp. fx (most agents don’t meet this ideal)

good analgesic

good muscle relaxant.

Question 11

IV anaesthetic agents- specific drugs

Answer 11

Propofol

Steroid anaesthetics i.e. alfaxalone

Barbiturates i.e. thiopentone and pentobarbitone

Imidazole derivatives i.e. etomidate

Dissociative agents i.e. ketamine, tiletamine

Question 12

Mechanism of action of induction agents- Propofol

Answer 12

Chemically unrelated to others (hindered phenol- phenol is a cyclic saturated 6-C molecule and is very caustic. hindered phenol has side chains and is less caustic).

Oil at room temp (formulated as an emulsion)

enhanced GABA transmission (increased flux of Cl-), similar to BZP but at a different site

As rapid as thiopentone

short acting, smooth and rapid recovery

suitable for TIVA

Question 13

Propofol pharmokinetics and metabolism

Answer 13

highly protein bound (98% plasma-protein bound), but very lipid soluble

large volume of distribution (>3L/kg–beyond total body water)

redistribution and metabolism- you administr dose, rapidly circulates and crosses BBB–>CNS. As it continues circulating, it accumulates in lipid tissues. Not a huge problem because it’s metabolised very rapidly–can top up dose as needed.

Metabolised at liver and another site (suggestion that it’s the lungs)- metabolism happens in the liver but not enough happens there to metabolism ALL the propofol

Conjugated (sulphate and glucuronide) prior to excretion in the urine

rapidly cleared (>40 ml/kg/min)

Question 14

Alfaxalone

Answer 14

steroid anaesthetic agent- insoluble in water, presented in cyclodextrin vehicle

Enhances inhibitory action of GABA- also, it possibly inhibits nicotinic ACh receptors and noradrenaline uptake

Advantages: high therapeutic index- as a group, GAs have narrow index

rapid induction

rapid metabolism

suitable for TIVA- short acting, good recovery

Question 15

Thiopentone- mechanism of action

Answer 15

thiopentone=barbiturate

reversibly depress activity of all excitable tissue

reticular activating system is particularly susceptible

enhance inhibitory action of GABA- allosteric site (not same site as GABA, but another binding site on the receptor); promote binding of GABA to GABA-a receptor, enlarge GABA-induced chloride currents.

Question 16

Barbiturates- pharmokinetics

Answer 16

Characteristics: weak acids (sodium salts, pH>10) need allosteric solution for administration

>60% unionized in blood

>80% plasma protein bound- good distribution though d/t lipid solubility

repeat administration results in accumulation in fat stores

Metabolism: heptic oxidation, conjugation, renal excretion

half life= 8 hours- long time to clear drug

NOT good for TIVA

Question 17

Redistribution

Answer 17

surgical anaesthesia- rapidly, drug gets sequestered into fat sores, draws out of brain. later, almost all drug is still in the body, just not at the brain. if you want to top up, you can saturate the fat stores–>very long state of anaesthetic hangover.

Question 18

Etomidate

Answer 18

imidizaole derivative

potent, short acting non-barbiturate

similar to thiopentone

enhance inhibitory action of GABA

rapid induction/recovery

poor quality of anaesthesia– muscle hypertonicity, hyperexcitability on recovery.

Question 19

Ketamine

Answer 19

dissociative agents

sensation of dissociation- 15 seconds; unconsciousness- 30 seconds; lasts 10-15 minutes

Mechanism of action: interrupts the association between limbic and cortical regions by acting on NMDA receptor (excitatotory) ion channge which receptor is intergral part of. inhibits NMDA receptors

Ketamine can physically block the open ion channel but it also decreases frequency of opening by binding modulatory sites.

Question 20

Clinical aspects of propofol pharmokinetics

Answer 20

pharmocological effect may be enhanced in hypoproteinemia

propofol is highly protein bound. may get enhanced anaesthetic effect if patient is hypoproteinemic because FREE drug is responsible for effect.

Pharmacological effect is NOT prolonged if 1) repeated IV doses are administered (i.e. it’s suitable for maintenance in dogs because it’s rapidly metabolsed) 2) in dogs with hepatic dysunfction because it’s capable of metabolism elsewhere besides liver. don’t see prolonged elimination even with dogs with hepatic dysfunction

nb: a prolonged effect may be seen in cats. cats don’t metabolise phenol very well–> not used for maintenance in cats or in cats with hepatic dysfunction

Question 21

Propofol effects on CNS

Answer 21

rapid loss of consciousness without specific analgesia( not blocking nociceptive pathway)- ~5 minutes duration– long enough for induction

Reduced cerebral blood metabolic rate and blood flow- benefical effects under anaesthesia, decreased metabolic products, less need for oxygen and nutrients

decreased intracranial pressure–this is good because too much Q to brain leads to increased intracranial pressure

Anti-covulsant action- can be used in some circumstances to prevent seizures.

Question 22

Propofol effects on CV system

Answer 22

transient fall in BP due to vasodilation and mild myocardial depression (not a huge amount clinically)

heart rate usually unchanged

take care in shocked/hypovolemic patients–see much more dramatic CV effects. normally, BRR tries to compensate BP. propofol interferes with BRR.

not inherently arrhythmogenic- doesn’t sensitize heart to catecholamines

Question 23

Propofol effects on respiratory system and other organs

Answer 23

Respt: post induction apnoea is quite common- this is OK as long as you can support ventilation- more likely to see it if you give v. high doses v. quickly

Other organs: non-irritant if injected perivascularly

pain (cold) on injection reported in people (cats?)

occasional muscle twitching/rigidity of extensors

repeated use (i.e. on consecutive days) can cause oxidative damage to RBCs in cats (heinz body anemia)

Question 24

Clinical summary of propofol

Answer 24

used as an IV induction agent

occasionally used as a maintenance agent in dogs

used to treat status epilepticus in dogs

Licensed in dogs and cats

Caution in: shocked/hypovolemic patients, cats with hepatic dysfunction, cats requiring repeat anaesthetics

Question 25

Formulations of propofol

Answer 25

1. lipid emulsion: preservative free- problem= bacterial growth- grow well in lipid discard within 6 hours of opening (data sheet says throw out immediately) 2. lipid emulsion with preservative: "propoflo plus" with benzyl alcohol use within 28 days of opening Contraindications: prolonged infusion (\>30 minutes); do not give more than 24mg/kg per anaesthetic (=around 30 minutes) Be cautious if \<5 months of age, pregnant or lactating- not shown to be safe concern of build-up of benzyl alcohol causing toxicity.

Question 26

Alfaxalone effects on CNS

Answer 26

not v. many differences between propofol and alfaxalone rapid loss of consciousness without specific analgesia reduced cerebral metabolic rate, Q and IC pressure Anecdotal reports of muscle twitching and rigidity on induction or during recovery (uncommon)a

Question 27

Alfaxalone effects on CVS, respiratory system

Answer 27

CV: dose-dependent CV depression Clinical doses: mild hypotension primarily due to vasodilation (alfaxalone doesn't impair BRR cf. propofol) Cyclodextrin formulation is NOT associated with hisamine release (cf. Saffan=historical version of alfaxalone) Resp system: post-induction apnea does occur but not often- even less common than in propofol Recovery: occasionally poor quality, stormy recovery- particularly if you've had a short period of anaesthesia cf. propofol

Question 28

Clinical use of Alfaxalone

Answer 28

used as IV induction agent also used as maintenance agent for short anaesthetics in dogs (cats?) Licensed in dogs and cats (alfaxan)- used in rabbits off-license and sometimes used in horses, but it's not a greta idea previous formulation in cremophor (Saffan) caused life-threatening histamine release in dogs- only used in cats Little tissue toxicity if injected perivascularly- can be given IM, but less reliable (unlike propofol, which is NOT given IM).

Question 29

Thiopentone clinical use

Answer 29

Previously used as an IV induction agent- vet prep no longer available v. few indications: e.g. top-up anaesthesia in horses- deepens plane of anaesthesia Effects: accumulate if repeated doses given unconsciousness, decreased IC pressure and anticonvulsant mild decrease in BP and increase HR post induction apnea tissue necrosis if injected peri-vascularly due to strongly alkaline solution

Question 30

Pentobarbitone

Answer 30

very similar structure to thiopentone less plasma protein bound (40%) slow onset of action (cf thiopentone)- lower lipid solubility longer duration (30-45 minutes) in dog profound respiratory depression not recommended for anaesthetic use licensed only for euthanasia d/t narrow therapeutic index.

Question 31

Etomidate

Answer 31

probably not used often, altohugh sometimes used in cardiac disease occasionally used as an induction agent but no vet license. minimal CVS or resp. depression Can cause involuntary movement/muscle twitching (induction quality isn't great) pain on injection reported inhibits steroidogenesis--inhibits conversion of cholesterol to cortisol-- not a problem in a lot of patients but certain critical pateitns need stress hormone to deal with hemorrhage/sepsis.

Question 32

Dissociative anaesthesia

Answer 32

dissociative agents produce a different quality of anaesthesia. unlike blanket depression, get dissociation between cortex and limbic system. features include: sensory loss with specific analgesia increased muscle tone eyes open and slow nystagmus (esp. in horses) active reflexes incl. laryngeal/pharyngeal reflexes (palpebral reflex may still be patent) less profound CVS and resp. depression

Question 33

Ketamine effects on CNS

Answer 33

loss of consciousness with analgesia increased cerebral oxygen consumption and cerebral blood flow-- increased IC pressure- troublesome if head trauma or brain tumor convulsions in dogs/horses if used as sole agent hallucinations/emergence delirium-- agitated recovery-- dysphoria.

Question 34

Ketamine effects on other systems

Answer 34

Musculoskeletal: muscle tone may be increased CV: mild increases in BP, HR and CO Respiration: minimal effect- especially if in combo with other drugs

Question 35

Clinical use of Ketamine

Answer 35

never use as sole agent for anaesthesia typical uses: 1) to induce anaesthesia in dogs, cats and horses- combined with benzodiazepine and injected IV 2) to induce and maintain anaesthesia (~30 minutes) in dogs and cats: combined with alpha 2 agonist (+/- butorphanol) and injected IM 3) to provide analgesia in dogs and cats: much lower doses given IM or by IV infusion- can use ketamine alone in this context Licensed in dogs, cats, horses and primates Caution in patients with: elevated IC pressure, a history of seizures (can promote seizure activity), pre-existing tachycardia or animal in which tachycardia would be detrimental

Question 36

Total intravenous anaesthesia (TIVA)

Answer 36

anaesthesia maintained by intermittent boluses or continuous infusion -avoids risk to people administering drugs i.e. no enviro pollution easy to administer- implies without intubating but modern techniques in small animals use intubation known pharmacokinetics inhalational anaesthetics may be unsuitable in some individuals i.e. airway surgery or malignant hyperthermia.

Question 37

Ideal TIVA agents

Answer 37

ideal properites of iV agent, but also short-acting, rapidly metabolised and cleared (no accumulation), inactive and nontoxic metabolites Which agents are used? \*Propofol (preservative free form): caution in cats; no analgesia, CVS and respr. depression Propofol plus specfic analgesic (ketamine or fentanyl or alpha 2 agonist) Alfaxalone (in small animals)- likely need to combine with analgesic. Triple drip: alpha 2 agonist + GGE + ketamine- popular for field anaesthesia in horses

Question 38

Inhalational anaesthetics

Answer 38

typically used for maintenance of anaesthesia advantages: 1) delivery/elimination depends on ventilation- no hepatic metabolism/renal excretion requirements. easy to adjust anaesthetic depth- very rapdi adjustment Disadvantages: equipment required i.e. ET tube, carrier gas (O2), vaporiser, breathing system, etc; environmental pollution- leakage into immediate environment; volatile agents generates CFCs; NO can behave as greenhouse gases.

Question 39

Inhalational anaesthetic agents as induction agents

Answer 39

less commonly used to induce- usually when you can't get IV access Advantages: IV access can be secured after induction Disadvantages: environmental pollution; takes longer and delay in securing airway may be a problem in some cases (dyspnea/regurg.)

Question 40

Pharmacokinetics of inhalational anaesthetics

Answer 40

structure: small, lipid-soluble--cross alveolar membranes easily halogenated hydrocarbon: i.e. halothane halogenated ether: i.e. isoflurane (most of newer compounds) HC or ether have implications for metabolism

Question 41

Speed of induction/recovery of inhalational anaesthetic agents

Answer 41

Blood:gas partition coefficient: numerical value which describes where the substance would rather be. LOW blood:gas gives rapid induction/recovery i.e. in order to achieve equilibrium, not much of drug needs to move into blood. can achieve equilibrium rapidly. i.e. would prefer to stay in alveolar air. LOW blood:gas allows for rapid control Oil:gas partition coefficient: relates to lipid solubility. the more lipid soluble, the more rapid it reaches site of action HIGH oil:gas gives high potentcy Physiological factors: alveolar ventilation rate: speed at which patient is breathing cardiac output: speed at which blood is moving

Question 42

Metabolism and elimination of inhalational anaesthetics

Answer 42

elimination primarily by exhalation- helps control duration and reovery from anaesthesia. metabolism in liver- extent depends on the agent potential production of toxin metabolites- risks to patient and staff metabolism of drugs important not in duration of action but formation of metabolites.

Question 43

Minimum alveolar concentration (MAC)

Answer 43

MAC describes the minimum alveolar concentration at which 50% of patients will not respond to a particular stimulus, i.e how much of a drug needs to be in the alveolus which would render patient anaesthetized MAC compares the potency of different inhalational anaesthetics the lower the MAC, the more potent the drug is. lots of different factors that can influence MAC value

Question 44

Factors which can alter MAC

Answer 44

species age: mac lower in geriatrics and neonates (i.e. need less of an agent) pregnancy: mac decreased hypothermia: mac decreased d/t peripheral vasoconstriction drugs: premedicants can greatly reduce MAC

Question 45

Ideal properties of inhalation anaesthetic

Answer 45

stable on storage- halothanes don't meet this easily vaporized: volatile- want it to be easily vaporized nonflammable- ether=flammable non-irritant to airways and NOT pungent- might dissuade animal from breathing in undergoes minimal metabolism (non-toxic) compatibile with equipment incl. soda lime (CO2 absorbant- soda lime can interact/interfere with some agents) low blood: gas partition coefficient minimal adverse CVS or resp. effects good analgesic and muscle relaxant

Question 46

Individual inhalational anaesthetic agents

Answer 46

Volatile agents: _Halothane, isoflurane_, desflurane, _sevoflurane_ Gas: Nitrous oxide

Question 47

Halothane physical properties

Answer 47

chemical structure: halogenated hydrocarbon (impact on CV effect) Liquid: preparations contain preservative thymol- nb thymol can build-up in vaporizers- need to have halothane vaproziers clean. Vapor pressure (mmHg): 244 ---the higher the vapor pressure, the more volatile (i.e easily vaporized) MAC (%): 0.9 ---MAC value is pretty low (i.e potent) Oil: gas partition coefficient: 224 (pretty high, i.e. potent) Blood: gas partition: 2.5 (moderately low, moderately rapid rate of change of depth) % metabolised: ~20-- pretty high, potential to generate toxic metabolites.

Question 48

Halothane effects on CNS

Answer 48

dose dependent depression without specific analgesic action reduces metabolic O2 consumption potent cerebral vasodilator: increased blood flow, increase IC pressure, impaired perfusion--\> undesireable-- critical factor in head trauma or brain tumor.

Question 49

Halothane effects on CVS and resp. system

Answer 49

CV: hypotension(all agents cause hypotension- different mechanisms) depression of myocardial contractility (decreased stroke volume)--\> decreased CO--\>decreased BP minimal change in TPR sensitizes myocardium to catecholamines- dysrrhythmias more common in presence of halothanes- ethers don't tend to do this. Resp system: dose-dependent depression- apnea at ~2 x MAC ---usually clinically manageable

Question 50

Halothane effects on other organs

Answer 50

Liver: mild, transient dysfunction due to hypoxia- reflects effect on CO, decreased liver perfusion rarely, immune-mediated hepatic necrosis (consequence of metabolite binding to cells and trigger immune-mediated hepatic necrosis) Kidney: reduced blood flow Muscle: moderate relaxation (potentiates NMBDs (muscle relaxants) trigger for malignant hyperthermia- rare, life-threatening excessive release of Ca2+ from SR--\>muscle rigidity--\>heat--\>acidosis--\> pigs most likely.

Question 51

Clinical summary of halothane

Answer 51

licensed in NON-food producing animals potent moderate speed of induction/recovery relatively high rate of metabolism significant myocardial depression potentially arrhythmogenic use has declined rapidly in recent years.

Question 52

Isoflurance physical properties

Answer 52

Halogenated ehter (not as dysrrhythmic) Volatile liquid Vapor pressure: 240 (high- easily vaporized) MAC: 1.3 (slightly higher than halothane) Oil: gas partition: 91 (lower lipid solubility, therefore less potent than halothane) Blood: gas partition: 1.5 (lower than halothane- more rapid rate of change of depth) % metabolised: 0.2 (very low)

Question 53

Isoflurane CNS effects

Answer 53

Dose dependent depression without specific analgesic action reduces metabolic O2 consumption less cerebral vasodilation than halothane; still potential for increase in IC pressure. Responsiveness to CO2 retained. Ventilation drives CO2 level down, increases vasoconstriction to off-set increase in IC pressure. This doesn't happen with halothane.

Question 54

Isoflurance CV and resp system effects

Answer 54

Hypotension: related to peripheral vasodilation. CO maintained (except for deep plane anaesthesia); peripheral vascular resistance falls Less sensitisation to catecholamines Resp system: dose dependent depression, see a little more with isoflurane than with halothane

Question 55

Isoflurane effects on other organs

Answer 55

Liver: hepatic dysfunction less likely (cf halothane)- hepatic Q better maintained- better CO, better liver perfusion Minimal metabolism- decreased risk of getting toxic metabolites Kidney: reduced blood flow muscle: good relaxation (potentiates NMBs) trigger for malignant hyperthermia

Question 56

Clinical summary of Isoflurane

Answer 56

cf. halothane Licensed in non-food producing animals faster speed of induction/recovery/change of depth pungent odor (not ideal for induction) minimal metabolism CO better maintained less arrhythmogenic most widely used inhalational agent

Question 57

Sevoflurane- physical properties

Answer 57

Halogenated ether; voltaile liquid Vapor presure: 170 MAC: 2.3 Oil: gas partition: 47 (not very potent, less lipid soluble) Blood: gas partition coefficient: 0.68 ---very low, even faster rate of change of depth % metabolised: 3 -pretty low

Question 58

Sevoflurane organ system effects

Answer 58

Similar to iso in most respects CV: increases in heart rate less likely (c.f iso and deslurane) resp system: minimal airway irriation- less aversive smell Kidney: concern of fx on kidney when it first came out. product of metabolism F- potentially nephrotoxic reacts with soda lime (CO2 absorbant) to yield COmpound A which is nephrotoxic in rats, but not shown to be nephrotoxic in any other animal. If existing kidney disease, consider not using sevoflurane.

Question 59

Clinical summary of Sevoflurane

Answer 59

licensed in dogs rapid induction/recovery/change of depth pleasant odor and minimal airway irritation- suitable for induction low rate of metabolism care in patients with existing renal insufficiency

Question 60

Desflurane- physical properties

Answer 60

least important, no veterinary license halogenated ether Boiling point= 23 degrees C (need specialized vaporiser) Vapor pressure- 669 (very vey volatile) MAC %: 7.2 Oil: gas- 19 (reduced lipid solubility- much less potent) Blood: gas- 0.42 (rapid change of plane, onsent and recovery) % metabolised: 0.02

Question 61

Desflurane CV and resp effects

Answer 61

Similar to iso in most respects CV: rapid increases in inspired concentration can increase HR and arterial BP (catecholamines) Resp system: high inspired concentrations can cause airway irritation

Question 62

Clinical summary of desflurane

Answer 62

no veterinary license low potency fastest speed of induction/recovery/change of depth airway irritation (not ideal for induction) minimal metabolism used in people for "day-case" surgery not yet widely used in vet med, but could be useful where you need rapid recovery i.e. in brachycephalic patients.

Question 63

Methoxyflurane physical properites

Answer 63

Older agent vapor pressure: 23- difficult to vaporize MAC: 0.29 (very very potent) Oil: gas 970 blood: gas 15 --slow onset/recovery/rate of change of depth % metabolised: very high halogenated ether potentially nephrotoxic metabolite.

Question 64

Nitrous oxide- physical properties

Answer 64

N2O Colorless gas, without taste or odor stored under pressure in cylinders Mac% \>100 ---over 100%, can't anaesthetize with NO alone Oil: gas 1.4 ---not potent, very low lipid solubility Blood: gas 0.47 -- rapid onset/recovery/rate of change % metabolised: \<0.01

Question 65

Nitrous effects

Answer 65

Organ systems: generally minimal CNS: provides specific analgesia- NMDA receptor antagonist- blocks central sensitization Side effects: prolonged low-level exposure inactivates vitamin B12 dependent enzymes--\> bone marrow suppression, defective myleination causing polyneuropathy teratogenic- can cause birth defects.

Question 66

Clinical use of NO

Answer 66

used as an adjunct, not as sole agent: use of 50-75% of N2O has sparing effect on volatile agent--\> need less isoflurane Must have minimum of 30% oxygen + isoflurane or sevoflurane, otherwise patient becomes hypoxemic Used to speed induction 2nd gas effect: high volume of uptake of nitrous oxide has "concentrating" effect on volatile agent in alveoli--\>speeds on set Also, N2O has low blood: gas partition coefficient. Diffusion hypoxia at end of anaesthesia: N2O diffisues back into alveoli lowering arterial partial pressure of oxygen. Provie 100% oxygen for 10 minutes after N2O turned off. Caution: expands gas filled cavities Contraindicated in ruminants, GDV, pneumothorax etc.