---start---- anesthesia 3/24 soma I got here at about 1:20, sorry. factors controlling induction: alveolar ventilation cardiac output solubility of anesthetic agent in blood something else i didn't hear uptake curves of various anestheti agents - page 4 of handout. nitrous, sevoflurane, isoflurane, halo, metofane. plots the % of inspired concentration vs time. methoxyflurane is very potent - mac about .23; induction is very slow with methoxyflurane. nitrous, mac is 188; induction is very rapid. sevoflurane - mac is 2, induction also very rapid. induction - % of inspired concentration reaches equilibrium in alveoli and CNS rapidly with nitrous, sevoflurane, slower with methoxyflurane, in the middle with halothane. so if you start by giving 1 MAC of sevoflurane, the inspired and alveolar concentrations equilibrate quickly - this is the goal of anesthesia. you start with a specific concentration,a nd you want alveolar concentration to approach inspired concentration as quickly as possible. once this has occured, and you reach 1.3 MAC, you're at the surgical plane. how do you get to that point? all things being equal, alveolar ventilation, cardiac output, size of patient,etc - the determination of how quickly you get to the point you need has to do with solubility of the agent of blood in tissue. step back and before we go into relative solubility - functional residual capacity (FRC) - relationship to tidal volume. we'll talk about FRC a lot. what's that? the volume of gas left in the lung after a normal exhalation- not a forced exhalation. if you take a lung out and put it on the table, and let it exhale,and take a syringe and try to suck gas out, will you be able to get all the gas out? no, b/c you will collapse the small airways. residual volume is part of functional residual capacity. simple model of pulmonary system: there's no pulmonary blood flow that removes anesthetic agent. two factors determine turnover in lung- alveolar ventilation and FRC - you need to wash out gas in alveoli and replace it with fresh gas. fresh gases are oxygen, the inhaled anesthetic, +/- nitrous oxide. Lung Model - 1 assume lung is bellows - that thing you use on the fireplace. when you collapse it down to zero volume, changeover rate is one breath - squeeze it all out, get all new stuff in - because there is no FRC in the bellows. lungs are not that way, though. you can't get rid of all the gas and replace it with one breath. think about what's happening when you are doing this - you have to remove a volumeand replace a volume in an incremental manner - a wash in wash out situation. so there is an exponential, step wise increase in your final concentration - there is a certain rate of change of the alveolar concentration - similar to the half life process of drug concentration in blood. if you took a one liter volume of water and put in a thimblefull of blue dye, the color in the container would change dramatically. take out one drop, add in a new drop of dye, color change is less dramatic - do it over and over, color keeps changing, but less of a change each time. when it's dark, and you add a new drop, the color change is very little. this is what's going on. there's a point up where you reach a plateau, where the gas in alveoli is 99.9% inspired concentration. then, the FRC, rate of ventilation, and tidal volume will determine how quickly you replace the existing gas in the lung (inspired gas plus water vapor plus nitrogen plus CO2 and a little oxygen and any other pollutants that you may have inhaled.) you inhale 20% O2, exhale about 16%; exhale about 5% CO2, exhale a little less than 80% N2, water vapor also in there. you humidify the room air and saturate it with water vapor in the lung. 5% CO2 --> PaCO2 in alveoli of 40 mmHg so we replace this exhaled gas, primarily nitrogen and oxygen, with 100% O2 and anesthetic agent. you are washing out nitrogen, mainly. you're not washing out Co2 because that'spart of metabolic process. you're basically washing out nitrogen and replacing it with oxyggen. earlier we were told about not closing the system down until you've washed out the nitrogen, because the system is a circle, and if you don't flush the circle, animal will rebreathe the nitrogen back in - because it exhales back into the circle. if the animal breathed out to the world,washout would be faster. volume/flow relationships: volume/flow relationship of lung is the time constant K of lung a volume of 20 L (FRC of horse) and flow 20 L/min (kind of low) K= 20L/20L/min = about 1 minute K = TC = FRC/alveolar ventilation so if K = 1 minute, it takes aobut 5 minutes to equilibrate - about 5 half lives, or 5 time constants. so alveolar ventilation relative to FRC is important for induction. so if you give a thiobarbiturate, and drop RR to 4 bpm, induction with gas takes longer this will happen too all of us: and in student surgery it will happen and someone will be standing over you asking you these questions. when you are giving anesthesia, you're alone, and someone is hovering over you and someone asks you something, you don't have time to go look it up - you have to know the answer. so think about emergencies that might occur before they occur. if you double the respiratory minute volume or alveolar ventilation, you will halve the time it takes to get to equilibrium. if the animal stops breathing during induction, you can't induce anesthesia, so you have to ventilate the animal yourself - assist it or control it - squeeze the bag, providing alveolar ventilation. wash in and wash out curves - these are basically mirror images of one another. this assumes all other parameters are equal. what does cardiac output have to do with this? well, to induce anesthesia, you have to have alveolar ventilation and cardiac output - to move drug to body tissues from alveoli and from tissues to alveoli for recovery. CO and where stuff is going relative to size of animal is what is important here. we're adding something, and delivering it around. this is simple [ha bloody ha ha] blood gas coefficient: ratio b/w blood and and gas concentration at equilibrium. the relative solubility of the anesthetic agent in blood and tissue determines how rapid the induction is. it has nothing to do with the potency. all of these drugs are soluble in body tissues and move across membranes very easily, but there are relative differences. you determine this pretty straighforwardly. you have a container, and you have an in and an out. you put blood into it. you find a way of mixing it up. you have a thin film of blood in there. you put in 1% of stuff. you equilibrate a film of blood with that known concentration. now, if you have 2.5 parts of drug in blood, and 1% coming in, then solubility is 2.5. in alveoli, if there is 1% coming in (of halothane) then you have 2.5% in plasma. this is lambda. for methoxyflurane, lamda is 13 - for 1 part in alveoli, there are 13 parts in plasma. if your lambda is 1, it's 1:1, if it's 0.5, you have 1/2 as much in plasma as you do in alveoli. so methoxyflurane is more soluble in plasma than sevoflurane or nitrous oxide. therefore, therefore, the induction of anesthesia with nitrous oxide is much more rapid than for methoxyflurane. the gases iwth lower relative solubility have faster induction. this is almost opposite the thiobarbiturate, with the exception that we're giving a bolus IV, fairly rapidly, so the solubility helps it move across into CNS rapidly. it's the same situation here, with the exception that you are giving an infusion instead of a bolus, and then waiting for anesthesia. the more soluble the drug, the slower the induction. a drug that's less soluble will have faster induction. this is important when you're trying to control anesthesia. if you have hypotension, respiratory compromise - the more soluble agent you can dump more quickly, rapidly reduce concentration in body - that's wrong, he meant less soluble, I'm sure. ---end---