3. Inhalational Agents Flashcards
Sevoflurane
MAC
Metab by
releases
Mac 2.5
By P450 2E1 to hexafluoroisopropanol and the release of inorganic fluoride ions.
Enflurane
B:G
Mol wt
BP
blood:gas partition coefficient - 1.8
Wt - 184
BP 56.5
Isoflurane
B;G
Mol wt
Blood g 1.4
Mol wt 184
Desflurane
B:G coeff
Problems
fluorinated methyl ether
approximately one-fifth the potency of isoflurane.
All volatile anaesthetic agents are weak calcium channel antagonists and therefore potentiate neuromuscular blocking agents.
It has a boiling point of approximately 23°C
The induction of anaesthesia can stimulate the sympathetic system as can change in inspired concentrations.
MAC 4-6%
B:G 0.42
way irritation leading to coughing, apnoea and laryngospasm
Halothane
B:G
BP
B;G 2.4
BP 23.5
Type 1 halothane hepatitis is characterised by a transient derangement of the liver function tests together with an acute hepatitis on histology. It may resolve without treatment and has no long term side effects.
Type 2 halothane hepatitis is thought to have an auto-immune aetiology and has a significant mortality.
Thymol is a preservative added to halothane, which accumulates on the wicks and effects the efficiency of the vapouriser if it is not emptied regularly.
MAC increased by
Hyperthyroidism
hyperthermia
MAC decreased by
Hypotension
Hypothermia
Hypoxia
HPV inhibited by
no effect
Agents that inhibit HPV
Ether
Halothane
Desflurane (>1.6 MAC)
Salbutamol
Agents with minimal or no effect on HPV
Thiopentone Fentanyl Desflurane (1MAC) Isoflurane (<1.5MAC) Sevoflurane (1MAC) Propofol.
Oil gas coeff & mac of Desflurane Isoflurane N2O Sevo Xenon
The physicochemical properties of all drugs influence pharmacokinetic behaviour in vivo.
Oil/gas (MAC) Desflurane 18 6 Isoflurane 90 1.2 Nitrous oxide 1.4 104 Sevoflurane 53.4 2 Xenon 1.9 71
Clinical potency is measured using the minimal alveolar concentration (MAC).
The anaesthetic agent with the highest oil:gas partition coefficient has the lowest MAC.
Halothane hepatitis
Minor derangement in liver function tests to fulminant hepatic failure.
appearance of liver damage within 28 days of halothane exposure
Seventy five per cent of patients with halothane hepatitis
avoided if:
Previous exposure has occurred within three months
There is known adverse reaction to halothane
Family history of adverse reaction
Pre-existing liver disease.
Halothane increases cerebral blood flow but reduces intraocular pressure.
MH & triggers
`Life threatening autosomal dominant condition linked with other myotonic disorders
Intracellular calcium transport is deranged with generalised muscular contraction generating excess heat.
Trigger
Sux
Inhaled agents - Trichloroethylene, cycloprop
Rx Dantrolene
Haloperidol - NLMS -Rx dantrolene also / bromocriptine
MAC is
(MAC) is defined as the alveolar concentration required in order to prevent movement to a standard surgical stimulus in 50% of unpremedicated patients at a pressure of 1 atmosphere.
Meyer-Overton hypothesis
Meyer-Overton hypothesis states that potency (lipid solubility) is proportional to the oil:gas partition co-efficient. The relationship between log oil:gas partition coefficient and MAC is linear with a high oil:gas partition coefficient equating to a low MAC (higher potency).
The blood:gas partition coefficient
The blood:gas partition coefficient is a measure of the solubility of an anaesthetic agent in blood. The lower the solubility, the greater the partial pressure it exerts and the faster the onset.
Nitrous Oxide
affect on cerebral
flow
metab
Affect on NMDA
Affect on CO2 reactivity
Whats the second mssgr
causes direct cerebral stim=
increases cerebral blood flow.
Increased metabolism specifically in the frontal lobes and limbic system =
increases the cerebral metabolic rate of oxygen consumption (CMRO2).
Cerebral autoregulation is impaired
used with propofol maintained.
Nitrous oxide antagonises NMDA receptors (it is not an NMDA agonist), which may result in neurological damage, but this effect may be limited by the concurrent use of GABA agonists or inhalational anaesthetics.
Carbon dioxide reactivity remains unaffected.
Cyclic guanosine monophosphate (cGMP - 2nd messenger
Xenon
Inert gas
not negatively inotropic
Not cause vasodilatation.
Xenon gives rapid induction and recovery,
low blood/gas solubility coefficient (0.115),
MAC of 71%
boiling point is −108°C
oil/gas solubility coefficient of 1.9.
Its low blood solubility can cause diffusion hypoxia if supplementary oxygen is not provided at the end of anesthesia.
Xenon:
Has a low toxicity
Is not teratogenic
Is not metabolised within the body, and
Is not a trigger for malignant hyperpyrexia.
Several studies have shown that xenon exhibits neuroprotective properties without co-existing neurotoxicity by protecting neural cells against ischaemic injury.
Xenon is produced as a by-product of the fractional distillation of liquid air and is an expensive process and is thus delivered in closed circuit breathing systems.
Xenon-133, unlike elemental xenon, is a radioactive gas produced by fission of uranium-235, which is used in diagnostic inhalational tests.
Ideal volatile agent for an inhalational induction
Pleasant smell and not pungent
Not irritant to the respiratory tract, that is, induces breath-holding, coughing or laryngeal spasm
Rapid onset and offset of action. (e blood:gas partition coefficient)
Blood gas coeff of common inhal
Halothane 2.3 Isoflurane 1.4 Sevoflurane 0.6 Desflurane 0.45 Nitrous oxide 0.47
Penthrox
what the blood gas coeff
mac
svp
properteis
metab
safe upper lim
Methoxyflurane - halogen ether
high blood gas - 16 - slow
Mac .16
SVP 49 @20
Non iritant, min fx systyemic
Neprhotx - lipid solubility
Pehtnrox = .3 mac hours
onset 4-5 min
50% hepatic meatb
Fluoride ion -
Neprhotox - safe lim 2mac hours
Up to 50% of methoxyflurane undergoes hepatic metabolism. The principal metabolites are fluoride ions, dichloroacetic acid and oxalic acid. Recent studies have shown that methoxyflurane also undergoes significant metabolism to fluoride within the kidney itself. The oxalic acid and fluoride are both nephrotoxic. The safe upper limit of exposure to methoxyflurane is 2 MAC-hours, which gives a serum fluoride level of 40 μmol/L, below the threshold for toxicity.
Methoxyflurane (PenthroxTM) is delivered from a self-administered inhaler with a volume of 3 mL that provides 25-30 minutes of analgesia with continuous use (intermittent use extends the duration of action).
The maximum exposure from a single methoxyflurane inhaler device is 0.3 MAC-hours, while the maximum recommended dose for analgesia of five inhalers a week
The onset of analgesic effect is 4-5 minutes.
MAC
Unaffected by
Increased by
Decreased by
Unaffected Gender Acidaemia Alkalaemia Body weight Serum potassium variations and The duration of the anaesthetic.
MAC is increased in:
Infants/children Hyperthermia Hypermetabolic states Sympathetic increase and Chronic alcoholism.
MAC is reduced in:
Hypothermia
Hypoxaemia
Old age
The presence of other depressant drugs,for example, opioids and
When the central nervous system has low levels of catecholamines, for example, alpha methyl dopa.
Carbon dioxide (levels >120 mmHg) has been used an anaesthetic - Hickman, which by an additive effect can be considered as decreasing MAC. On the other hand a markedly elevated CO2 (and even severe acidaemia) can stimulate the sympathetic system/release catecholamines and result in MAC increasing.
N2o manufactured by
What impurities formed
How reomoved
Examples of impurities
problems with the impurities
How do we test for these impurities
Problems with prolonged use of N2O
heating ammonium nitrate (not nitrite) to 240°C.
Ammonia
Nitric acid
Higher oxides of nitrogen),
Removed by passage through scrubbers and washers.
The higher oxides of nitrogen which are formed include:
Nitric oxide (NO) Nitrogen dioxide (NO2) Dinitrogen trioxide (N2O3) which decomposes to NO and NO2.
Irritant Respiratory tract -
pulmonary oedema hours
severe fibrotic reaction may occur after several weeks, which destroys the lung tissue.
Tested for contamination
Higher oxides of nitrogen,
Exposing moistened starch-iodide paper - gaseous contents of a cylinder, which turns blue if contaminants are present.
Prolonged use of N2O is associated with many side effects including the inhibition of methionine synthase, which results in bone marrow depression and a megaloblastic anaemia (not microcytic).
GWP100 of the following gases are as follows:
What is GWP100
What is it for Co2 Sevo iso des sevo methane
The inhalation halogenated anaesthetic agents, isoflurane, sevoflurane, and desflurane absorb infra-red radiation within the range of 7-10 µm and have a significant GWP100. The Carbon dioxide 1 Methane 23 Sevoflurane 130 Nitrous oxide 310 Isoflurane 510 Desflurane 2540
The approximate percentage metabolism of the volatile agents is as follows:
Halothane Iso En sevo des
Desflurane 0.02%.
Isoflurane 0.2%
Enflurane 2%
Sevoflurane 3-6%
Halothane 20%
Halothane effect on vasoconstriction cerebral vs iso
BP
SVP
Affect on myocardium
MAC
Halothane causes less cerebral vasoconstriction than isoflurane, which explains why isoflurane is popular in neuroanaesthesia.
Halothane boils at 50°C and has a saturated vapour pressure (SVP) of 32.3 kPa. The SVP is almost identical to isoflurane, and this may allow them be delivered using the same vaporiser, for example, Oxford miniature vaporiser.
All volatile agents inhibit hypoxic pulmonary vasoconstriction and therefore increase shunting.
Halothane sensitises the myocardium to circulating catecholamines and this is one reason why surgeons usually ask the anaesthetist prior to infiltrating epinephrine (adrenaline) containing local anaesthetics.
Drop SVR 18%
barorec reflex decerease
ganlgiong blocking
central vasomot depressant action
The minimum alveolar concentration (MAC) of halothane is 0.7% (not 1.15%).
Halothane absorb Uv + IR -
causes change elsaticity of silicone rubber
can be determ using refractormer
Mol wt 197 vs N2o 44
Convert MAC to PP
The partial pressure of a gas is proportional to its concentration, therefore, by transforming the MAC values for the volatile agents into partial pressures at 1 atmosphere (or 760 mmHg):
MAC (Volume %) = ( partial pressure of volatile agent (x) / 760mmHg )x 100
Halothane for example = 0.75 =( x/760)x100
x=(0.75 x 760)/100 =5.7mmHg
Age related mac partial pressures
Age related MAC for 40-year-old patient population
Halothane (MAC of 0.75%) has a partial pressure of 5.7
Isoflurane (MAC of 1.17%) has a partial pressure of 8.9
Enflurane (MAC of 1.68%) has a partial pressure of 12.8
Sevoflurane (MAC of 1.8%) has a partial pressure of 13.7
Desflurane (MAC of 6.6%) has a partial pressure of 50.2
Properties ideal anaesthetic
Phsyical
- Liquid Room temp
- High SVP - easy vape
- Low latent heat vaporisation
- Low specific heat capacity
- Chemically stable in light & heat
- Inert when in contact w/ metal rubber & soda lime
- Non flammable /explosive
- Long shelf life
- Inexpensive
10 No additives / preservatives - Environmentally friendly
- Non irritant/ nice smell
PK of Ideal inhalational
Low blood : gas coefficientg - fast onset
High oil partiation coeff - low MAC
Minimal metabolism - no Fl- prod
Excretion via lungs
PD Ideal
CNS Smooth rapid indcution Only affect cns Rapidly reversbily No increase CBF/ICP Analgesic Not epileptogenic
CVS
No depression
No sensation of myaocardium
No cor flow decrease
Resp
No breath holding laryngospasm
broncholidation
No resp depression
MSK
Releax
Non MH trigg#
GI
Anti emetic
Reanl haep haem
No effects / flow
not rterato
Onset is determined by
Blood: gas coefficient
Lower = faster
Potency
Oil:gas partition coeff
High - miore potent
Signif blood gas partition coeff
Ratio - amt anaes in blood to gas when equal vol in equil
PParadox a/w speed induction
Poorly soluble - high PP in blood - fast onset
Converse - solube -
rapidly enter blood - exert low PP
Slower onset
Effects related to PP in blood -> brain * not absolute amount present
Blood gas part coeff in order
Xenon .17 Des .42 NO .47 Sevo .68 Iso 1.4 En 1.9 Halo 2.3
Onset influenced
Blood gas coeff
Also - by mac
Alveolar vent /; irritability
Des - profound irritant
Equilibrium reached quicker with high or low blood g partition coeff
Reached more quick;y with those w/ a lower partition coeff
Factors influencing the speed appraoch equilibrium
Phsyiologty patient - factors related agents
High inspire conc - rapid increase PP alveoli - rapid onset
Increased alveolar vent - PP increase faster
FRC large - Inspoire conc dilute - opposite affect
CO - influces - low - more time for equilibration
incres onset
Conc grad mainatianed where COP increase - slower rise alveolar PP
Cocnetration effect & second gas effect
Concentration effect
NO 20x more solube blood vs O2 / N
High conc introduced - rapid upatke
Reduction in volume alveoli - NO extracted fast than N
Fract conc gas left in alveoli incrase = ‘conc effect’
