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inhalant anesthetics

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typically used to maintain anesthesia can be used to induce anesthesia- if administered vis a chamber or face mask very popular because of their safety- however older agents were not completely safe

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older inhalants- diethyl ether

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liquid, sweet odor very irritant to airways extremely flammable slow induction- very soluble

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older inhalants- chloroform

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hepatotoxic sensitizes myocardium to catecholamines

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older inhalants- cyclopropane

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inflammable- when mixed with O2= explosion cardiac arrhythmias

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older inhalants- halothane

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not available in IE anymore sensitizes myocardium to catecholamines

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older inhalants- methoxylurane

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potent analgesic slow induction and recovery extensive liver metabolism nephrotoxic- inorganic fluoride metabolites

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older inhalants- enflurane

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nephrotoxic

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inhalant anesthetics- advantages

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safe rapid action, elimination and recovery easy to prolong anesthesia minimal metabolism less cardiac sensitivity to catecholamines

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inhalant anesthetics- disadvantages

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expensive atmospheric pollution cardiopulmonary depression little or no analgesia

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methods of description

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three ways of describing the quantity of an inhalant concentration pressure mass

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methods of description- concentration

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volume % as a percentage of the total gas volume delivered displayed on the monitor

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methods of description- pressure

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as a partial pressure of atmospheric pressure- tension various units- mmHg, Torr, kPa

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methods of description- mass

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mg or gm

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chemical properties

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nitrous oxide- inorganic compound inhalant anesthetics- organic compounds halogenated hydrocarbons- halothane halogenated ethers- isoflurane

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physical properties

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vapor pressure- saturated vapor pressure solubility partition coefficients- blood gas solubility, oil gas solubility

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saturated vapor pressure - vaporization

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molecules of a liquid and gas are in constant random motion at a liquid gas interface some molecules will pass from the liquid into the gaseous state, while others will return to liquid the former transition is known as vaporization

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saturated vapor pressure - in a closed container and at a constant pressure

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SVP dependent on temperature vaporization of liquid will proceed until an equilibrium is reached at which time there is no further movement of molecules between phases at equilibrium, the gaseous phase is said to be saturated the pressure exerted by molecules of vapor is termed the SVP

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saturated vapor pressure - definition

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SVP measures the volatility of the liquid agent in the carrier gas SVP gives an indication of the ease with which a volatile agents evaporates the higher the SVP the more volatile the anesthetic is- it goes from liquid to gas more rapidly the lower the SVP the less volatile the anesthetic is

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saturated vapor pressure - allows anesthetists to

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generate known concentrations of vapor SVP dictates the maximum concentration of the anesthetic in the vapor that can exist at a given temperature the higher the SVP the greater the concentration of volatile agent that can be delivered to the patient

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saturated vapor pressure - to determine the maximum concentration of a volatile agent in vapor

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SVP is expressed as a percentage of barometric pressure at sea level- 760 mmHg isoflurane has an SVP of 240 mmHg at 20C 240/760 x100 = 31/57% maximum concentration of isoflurane that can be delivered at this temp is ~32%

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saturated vapor pressure - actual for isoflurane

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32% is dangerous this concentration is higher than what is required to induce or maintain anesthesia vaporizers mix the carrier gas (oxygen) with saturated vapor in a controlled ratio to deliver safe concentrations 1-5%

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solubility

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inhaled agents have different solubilities in blood, tissues etc compare the different agents using solubility coefficients

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solubility coefficient

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aka partition or distribution coefficient used to describe the solubility of inhalation anesthetics in a variety of different solvents is the ratio of the concentration of anesthetic in one phase compared to another describes the affinity of an anesthetic for one solvent phase relative to another- that is how the anesthetic agent will partition itself between the two phases after equilibrium has been reached blood gas solubility coefficient oil gas solubility coefficient

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solubility- gases and vapors

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are able to dissolve in liquids and solids if gas molecules are overlying a liquid they will diffuse into the liquid aka dissolve there is a net movement of the gas into the liquid this process will continue until an equilibrium is reaches between the dissolved gas in the liquid and the undissolved portion above the liquid

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solubility- at equilibrium

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there is no net movement of anesthetic molecules between the two phases - number of gas molecules entering the liquid equals the number leaving the partial pressure exerted by the anesthetic in the gas phase will equal the partial pressure in the liquid phase PPr agent in gas= PPr agent in liquid

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solubility at equilibrium- the total number of anesthetic molecules in each compartment will not be equal. it depends on

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chemical structure of gas solubility of the agent in the liquid partial pressure of gas nature of liquid temperature

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blood gas solubility coefficient

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high blood gas solubility- ether low blood gas solubility- nitrous oxide

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oil gas solubility coefficient examples

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high oil gas solubility- halothane low oil gas solubility- desflurane

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blood gas solubility coefficient importance

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important in anesthesia as the anesthetic solubility in blood is a primary factor of the speed of anesthetic induction and recovery

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blood gas solubility coefficient - measurement of the solubility of a substance in blood compares to gas (alveoli)

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poorly soluble - nitrous oxide (0.47) highly soluble- ether (12) at equilibrium the concentration in blood is 12x higher than than in the air breather by the patient parameter that pulls the drug from the alveoli into the blood

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blood gas solubility coefficient - the more soluble and agent is

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the slower its onset an offset this is because its effects on the CNS depend on its partial pressure in blood/alveoli not on the absolute amount dissolved in blood

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blood gas solubility coefficient - high blood gas solubility- ether 12

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agent in the blood- more agent dissolved in the blood, more agent is therefore required to saturate the blood agent in the alveoli- as the molecules within the alveoli are readily taken up into the blood, the alveolar concentration and partial pressure remain low, concentration of the agent in the alveoli builds up slowly final effect- it takes longer to reach equilibrium between alveoli and blood, longer time before the partial pressure is increased

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blood gas solubility coefficient - low blood gas solubility - nitrous oxide- .47

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agent in the blood- less agent is dissolved in the blood, less agent in therefore required to saturate the blood agent in the alveoli- the amount of molecules within the alveoli that are taken up into the blood is low, the alveolar concentration and partial pressure is high, concentration of agent in the alveoli builds up fast final effect- it takes shorter time to reach equilibrium between alveoli and blood, shorter time before the partial pressure is increased

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what induced faster anesthesia

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the level of partial pressure

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minimum alveolar concentration MAC

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minimum concentrano of an anesthetic agent in the alveoli at which 50% of patients will not exhibit gross purposeful response (movement) to a particular surgical stimulus, usually at skin incision or tail clamping a measure of potency- the greater the MAC the more agent is required to produce anesthesia- therefore the lower its potency

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oil gas solubility coefficient

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measurement of lipid solubility indicator of potency it is inversely related to MAC the greater the lipid solubility of the inhaled rug, the greater the potency- the less is required to achieve an anesthetic effect, the lower the MAC is

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oil gas solubility coefficient- desflurane

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low oil:gas 19 low potency high MAC

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oil gas solubility coefficient- halothane

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high oil:gas 224 high potency low MAC

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summary - SVP at 20C

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volatility of the agent high SVP (desflurane 669mmHg)- high volatility an high concentration can be delivered low SVP (isoflurane 224 mmHg)- low volatility and lower concentration

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summary - blood gas solubility coefficient

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onset of action high (halothane 2.24)- slower onset low (desflurane 0.42) - faster onset

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summary - oil gas solubility

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potency, inversely related to MAC high (halothane 224, MAC 0.9%)- higher potency, lower MAC low (isoflurane 98, MAC 1.3%)- lower potency, high MAC

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factors effecting speed of induction- aim

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reach an adequate partial pressure of anesthetic in the brain

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anesthetic agents move down a partial pressure gradient

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from high partial pressure to lower partial pressure until an equilibrium is reached

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PA

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partial pressure in alveoli is a balance between anesthetic input and loss of agent

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Pa

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partial pressure in arterial blood

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the main determinant of speed of induction

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PA PA and Pa equilibriates rapidly Pa and P in brain quick equilibrium PA control P in the brain rapid rise in PA -> rapid onset

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to increase speed of onset- increased alveolar delivery (input)

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increased inspired aesthetic concentration- increases vaporizer dial setting, increased fresh gas flow, increased vaporization of the agent, decreased gas volume of patent breathing circuit increased alveolar ventilation- increased minute ventilation, decreased FRC/dead space ventilation

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to increase speed of onset- decrease removal from alveoli (loss)

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decreased BG solubility decreased cardiac output decreased tissue solubility

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increased alveolar delivery (input)- decreased FRC/ dead space

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functional residual capacity of the animal volume of air left in the lungs at the end of passive expiration acts a reservoir lower FRC= faster onset of anesthetic

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decreased removal from alveoli- decreased BG solubility

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agents with a low blood gas coefficient are associated with a more rapid induction of anesthesia

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decreased removal from alveoli- decreased cardiac output

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decrease CO tends to hasten anesthetic induction the lower the blood flow through the lungs, the lower the uptake of anesthetic molecules from the alveoli and the faster the rise in PA thus induction may be fast in a shocked patient but slow in an excited patient

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decreased removal from alveoli- decreased solubility in tissues

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anesthetic gases that are relatively insoluble in the tissues are associated with a more rapid induction of anesthesia uptake of anesthetic from the blood and into tissues maintains the diffusion gradient between the alveolar air and the blood the more anesthetic molecules most then diffuse out of the alveoli slowing the rise in alveolar partial pressure for agents that are poorly soluble in the tissue, equilibrium is reached at an earlier stage when relatively few molecules have diffused into the tissue and therefore the effect on alveolar partial pressure is minimal

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inhalant agent - CNS effects

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CNS depression increase in blood flow to the brain

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inhalant agent - CVS effects

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decrease in blood pressure and tissue perfusion vasodilation decrease in cardiac contractility decrease in heart rate renal and cerebra perfusion may be compromised increased sensitivity to catecholamines (halothane) - arrhythmia

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inhalant agent - respiratory effect

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depress ventilation hypoventilation results in respiratory acidosis (increased CO2)- decrease pH increased blood flow to the brain

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isoflurane - characteristics

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halogented ether supplied in brown bottles pungent odor- not recommended for mask or chamber induction

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isoflurane - pharmacokinetics

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B:G coefficient 1.46 very potent- MAC 1.28% only <0.2% is metabolized - good for animals with liver disease

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isoflurane - pharmacodynamics

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respiratory depressant- hypoventilation, irritation to airways CVS depression- reduction in blood pressure due to fall in systemic vascular resistance

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sevoflurane - characteristics

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halogenated ether not pungent odor- can be used for mask induction more expensive than isoflurane

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sevoflurane - pharmacokinetics

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less potent than isoflurane- MAC 2.36% B:G coefficient 0.68- faster onset and offset than isoflurane 2% metabolized

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sevoflurane -pharmacodynamics

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less respiratory depression similar CVS depression reacts with soda lime and baralyme to produce compound A- nephrotoxic , only in rats

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halothane- characteristics

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halogenated hydrocrabon sensitive to UV light- stored in brown bottles with preservative pleasant odor

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halothane- pharmacokinetics

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very potent- MAC 0.8% B:G coefficient of 2.54- slower onset and offset more metabolized in liver than newer agents- 20-25%

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halothane- pharmacodynamics

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respiratory depressant CVS- hypotension- reduction in heart contractility and rate, sensitizes myocardium- arrhythmias hepatotoxic not allowed in IE

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desflurane- characteristics

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halogenated ether pharmaco-dynamically similar to isoflurane expensive- requires special heated vaporizer

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desflurane- pharmacokinetics

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high vapor pressure- boils at ambient temperature, requires heated vaporizer to control output very low blood solubility - B:G coefficient 0.43 (fast onset) not very potent- MAC around 7.2-9.8% 0.2% metabolized- good

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desflurane- pharmacodynamics

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dose related respiratory depression and doesn't smell good irritation of airway- unpleasant to inhale does not sensitize the myocardium stimulation of sympathetic nervous system

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nitrous oxide- characteristics

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gas at room temperature supplied in cylinders - color coded blue

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nitrous oxide- pharmacokinetics

answer

not potent- MAC 200% it cannot be used as an anesthetic on its own, only used as an adjuvant B:G coefficient 0.47 (rapid onset of action)- not very soluble in blood no metabolism diffuses into closed gas spaces- due to low solubility coefficient diffusion hypoxia during recovery0 must be used with atlas 30% oxygen

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nitrous oxide- pharmacodynamics

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provides analgesia nonirritant to airways augments ventilation mild sympathetic stimulation risk of hypoxemia and cardiac arrhythmia

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nitrous oxide- concentration effect

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refers to the disproportionate rise in alveolar partial pressures of other gases N2O is much more soluble than N2 and O2 N2O diffuses out of the alveoli more rapidly than N2 can diffuse back into this results in reduced alveolar volume this results in a rise in alveolar partial pressure and concentration of the remaining gases

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nitrous oxide- second gas effects

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refers to the effect that N2O gases has on the speed of onset of anesthesia of the second gas- the volatile agent as a consequence of the concentration effect volatile agents achieves a rapid rise in alveolar partial pressure faster onset of action

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