----start---- 3/25/98 anesthesia soma ok, you're lying in bed, the alarm goes off, you look over and see it, leap out of bed, jump up - why don't you faint when you stand up abruptly from a horizontal position? Baroreceptors - in the aorta, the carotid (there's also chemoreceptor in the carotid) - the baroreceptors sense changes in pressure and try to correct for it. now, you have a dog under anesthesia, and he's in radiology, and you need to tilt his feet down. You say, sure, but there's a danger in doing that - what's the danger? he's lost reflexes - the baroreceptor isn't working well under anesthesia. this doesn't mean you can't move the dog's position, but you have to be aware that you may get some cardiovascular depression. valsalva maneuver - look it up. some folks weren't clear on the meaning of the uptake curves of various anesthetic agents. the chart is to show relationship b/w inspired concentration and expired concentration. early in induction, inspired concentration may be 2-3 times MAC (3-4% halothane, for example). the chart illustrates how rapidly the alveolar concentration approaches the inspired concentration, showing how rapid induction is. solubilities and MAC: halothane b/g 2.3, mac 0.88 metofane bg 10-13, mac 0.23 N2O b/g 180, mac 0.5 there is some relationship b/w blood/gas solubility and mac. the more soluble the drug is in blood, (and also if you looked at lipid solubility you'd see the metofane is highly soluble compared to N2O so there is a relationship b/w those two. (i know that's not a sentence but it's what he said) if you take oil, olive oil, and do the same thing with blood , you find that the amount of metofane dissolved in oil is high. so potency and solubility in fatty tissue are related. the more potent it is, the more soluble it is in a fatty medium. if that relates to anesthetic effect, we're not sure. N2O is inorganic, and it will produce stages of anesthesia, as will argon. divers are subject to nitrogen narcosis at depths where the pressure is 2-3 atmospheres. going back to more complicated lung model 3: before, we didn't remove blood or material from the lung through pulmonary circuit in our very simplistic models. we just looked at gas exchange. now, we're adding pulmonary blood flow. if you have no blood flow, you have the top dotted line on the graph - the concentration follows some exponential rise. if you start removing stuff from lung through pulmonary blood flow, it will rise to some level depending on the amount of material being removed. a moderate leak (solid line on chart) will acheive some kind of plateau, approaching a steady state. you're putting it in at a constant level, and removing it at some constant flow, so you do eventually reach a state where input and output are in equilibrium. if you have a larger leak, increased blood flow, you have a similar situation, with an earlier plateau. the "leak" is related to solubility of anesthetic agent. just envision that you have constant input of anesthetic agent, constant flow, constant alveolar ventilation, constant cardiac output, you change the solubility so more is removed per unit time, and the more soluble drug is represented by the bottom (large leak) curve, and a very minimal solubility drug like nitrous is represented by the top curve (no leak). remember, this is relative solubility. all these drugs move across membranes very quickly. p 10 of handout has chart. how do you build up a concentration in the CNS, blood, to put animal under anesthesia? uptake of anesthetics by blood and body tissues: -organs arent of equal size -blood flow to organs isn't proportional to size -solubility of anesthetic agents varies -solubility in tissues is proportional to solubility in blood but not identical -body tissues are placed into groups based on blood flow. highly perfused (brain, heart, kidney - visceral group), moderately perfused (muscle), low perfused (fatty) one compartment body model: remember that the pulmonary circuit is removing the anesthetic agent from the alveoli, distributing it to tissue. the more rapidly the tissues equilibrate with the delivered concentration, the greater the venous return, that is we talked about injectable drugs, that the AV difference across that organ, the more rapidly the arterial venous distance across the organ approaches zero, the venous return back to the lung increases rapidly, so alveolar concentration increases rapidly. if you want to build up an alveolar concentration - you're delivering and removing drug to/from lung at constant rate, and delivering drug to tissues. the more soluble the drug is in the tissue group - the longer it takes to equilibrate the tissue with the concentration you're delivering - meaning the venous return back to the lung takes a long time to build up - the AV difference will remain larger, it will not approach unity, simply b/c the solubility of anesthetic agent in this tissue is high. therefore tha mount of drug returning back to alveoli is low. the amount of drug going back to alveoli determines how rapidly alveolar concentration builds up. so it's your venous return with eventually higher concentrations of drug that aids in building up alveolar concentration. if this were a large sponge, and the brain were in this mass, you'd have to equilibrate the large body of tissue where the arterial concentration and alveolar concentration are similar, before the concentration returning back to the lung was sufficient for alveolar concentration was high enough for arterial concentration getting to brain was high enough to induce anesthesia. this is why solubility is related to speed of induction. think about it. drug gets to tissue, is absorbed, doesn't return to lung. difference b/w arterial and venous concentration is high. as the concentration difference narrows, the arterial concentration will increase, as more gets back to alveoli for arteries to pick up. go back to your uptake curves - how quickly your curve plateaus is related to speed of induction and solubility of agent in blood/tissues, and how much the tissues are sucking up the stuff and retaining it so that venous return is slow. very soluble agents take longer to induce anesthesia, I think is his point. going back to first diagram... lung model three - you never build up anesthetic concentration b/c nothing comes back to the alveoli to build up an increased concentration. as difference in concentration b/w arterial concentration and mixed venous concentration (mixed venous blood is found in the right atrium/pulmonary artery) narrows, alveolar concentrations rise more quickly. so the more rapidly you build up alveolar concentrations, blood is going from pulmonary arteries into veins and going to left side of heart and out to body - and more drug is getting to the rest of the body. so the less soluble a drug is in tissues, the faster you can build up a high alveolar concentration, and induce anesthesia.so if you turn the machine to 3 mac, the alveolar concentration won't be 3 mac until the venous return brings drug back for you.. if you start out with 1 MAC, how long will it take you to get to 1 MAC? (huh?) it's like starting an infusion. you don't start off by injecting a small amount - you start with a higher concentration, b/c it's redistributed. you start out with something higher than 1 MAC, therefore, to load the system. but if you did start with 1 mac, you'd get close to 1 mac eventually, but the time frame would depend on the solubility of anesthetic agent, all else (ventilation, cardiac output) being equal. for ether, methoxyflurane which are very soluble it would take a long time; for isoflurane, it wouldn't take so long. if you initially load the system, start at 3 mac, then bring concentration down to 1, will your alveolar concentration stay above 1? no. uptake is continuous. the tissues in which the brain is contained (highly perfused tissues) will equilibrate with an anesthetic concentration faster than other tissues, and when they reach equilibrium, the signs of anesthesia (pupils, respiration, heart rate, blood pressure, etc) are evident, and you reduce your concentration, because what you've done is started off with 2 or 3 or even 4 mac, and on the way to that level you've crossed the 1.3 mac point, and now you want to reduce your inspired concentration, to maintain your animal somewhere at the surgical plane. what happens if you simply turn off the system? now all you are delivering just oxygen. what happens? your arterial venous distance will increase, animal will redistribute drug from highly perfused tissue to muscle and fat and animal will wake up. the maintenance of anesthesia is really the continuous equilibration of tissue which isn't highly perfused. ok? that's how it works. it's as simple as that - if you understand what's happening to blood flow and relative flow to various tissues, you can understand why you can put an animal under anesthesia, because CNS is so highly perfused. multiple compartment body: p 12. you have a low flow, high flow, and moderate flow compartment (fat, cns/viscera, muscle) - this is the real situation. equilibration of body tissues - you have blood, vessel rich group, muscle group, fat group, and vessel poor group. once the vessel rich group equilibrates, difference b/w it and blood is very narrow, and that's where brain is. therefore, potency of agent isn't the point - that tells you the MAC you need. it's the solubility that determines how quickly you reach mac. the mirror image ofthat is speed of recovery - part of that involves how long you've been under anesthesia - the other part is how soluble that agent is. with sevoflurane there would be rapid recovery as drug was dumped from highly perfused tissue quickly - muscle and fat would contain small amounts. once you dump drug from highly perfused tissue you wake up. solubility of sevoflurane is very small. percent body mass and cardiac output: VRG MG FG VP body mass% 9 50 19 22 cardiac output 75 18 5.4 1.5 % cardiac output - schematic - p 14. shows cardiac output in proportion to blood flow and % body weight for heart, brain, liver, kidney, muscle, fat, skin/bone/ct. muscle is the biggest group based on body weight. note that fat proportion is variable with the individual. cardiac output to fat is low, but if there is more fat in the animal, then more drug is taken up per unit time and recovery will be a little slower. parts of uptake curve represent equilibration of various tissue compartments. the initial rapid rise in % of inspired concentration represents the uptake by highly perfused viscera. the knee of the curve is when the muscle tissue equilibrates, and the tail of the curve is the maintenance phase - see p 16. induction of anesthesia, how to beat the model. your goal is 1.3 mac - when you reach that point, you back off on your concentration - see p 17. we've talked about a constant alveolar ventilation and a constant cardiac output (CO). you've reached a plateau of 1.3 mac, animal is anesthetized. now CO increases. what happens to your plasma concentration and alveolar concentration of anesthetic agent? it will decrease. why? redistribution into less highly perfused tissue. as soon as you increase CO, you increase uptake by tissue. now you will equilibrate those tissues at a new perfusion level, so you have to increase drug delivery to keep your concentration up. (this is without an increase in ventilation. we're talking CO increases without increase in alveolar ventilation to compensate for it). what happens is you acheive your 1.3 mac, and cut back on anesthetic that you're delivering, but you haven't cut into the animal yet. now, you do cut into animal, and HR increases. you have to increase the amount of drug being delivered to compensate for the increase in CO causing decreased concentration in highly plasma concentration. if CO decreases, distribution decreases, alveolar concentration builds up, and concentration going to central compartment is higher. in the lung, as blood goes past, there is enough time for equilibration across the capillary, unless there is fibrous tissue or something that shouldn't be there. there is enough time to completely equilibrate with alveolar concentration. if that weren't so, we'd all be in deep trouble. we'd all be amoebas or something. what happens if you increase alveolar ventilation with constant CO? if you want to build up concentration quickly, you can increase alveolar ventilation by ventilating animal, increasing drug delivery per unit time. so you can speed induction this way. will that lead to any increases or decreases in HR? theoretically could cause a decrease in CO -which would speed induction even more by reducing distribution. you know the relationship of flows to induction of anesthesia. you must have a fairly high flow to induce anesthesia - 1% of drug at 3 L/min is more than 1% at 1 L/min - turnover in the circle is important also. once you induce and denitrogenate the animal, you can close down and deliver just over metabolic O2 requirement. if you ahve a GSD, O2 requirement is 100 ml/min at 1L flow, and in horse, O2 requirement is 2 L/min, proportional flow must be different. ----break--- Dr Klein Cardiac arrhythmias - an important cause of problems. consider that death is really a cardiac arrhythmia, or dysrhythmia - everyone has at least one cardiac arrhythmia in their life- when they die. an arrhythmia can be "the rude unhinging of the machinery of life" which we do not treat, or some pharmacologic or electrolyte interaction or abnormality, and those need treatment. you have to know they are there, and ID the type. Dr Klein hopes that we do better on the exam than other classes have done. remember, you need to know what part of the heart beat is causing what you see on the EKG. chapters 10 and 11 from Guyton were handed out before - make sure you have them and read them. also note that on the back of chapter 11 is a page added on from Dr Reef - explaining the differences in patterns of depolarization of ventricles b/w humans, dogs, small carnivores, large herbivores, and possibly other large mammals like marine mammals such as walruses or perhaps whales. the differences create differences in the EKG which you need to know about to know what lead system to use and so forth. start with a quick review - impulse initiation and propagation in the heart. remember the electrical impulse starts in the SA node in right atrium, then propagates across both atria and to AV node by special internodal pathways. at AV node there is a delay in impulse transmission. so the sinus node is a few cells that depolarize - if that's all that happens, what would you see on the EKG, if that impulse didn't propagate at all? well, if a couple tiny cells depolarized and created their own tiny action potentials, you'd see nothing on the EKG. if the impulse spread across the atria only, you'd see the P-wave - that little blip in front of the complex. ok, so then there's a delay across the AV node - you go from the internodal pathways through the transitional fibers into the AV node (note: the chapters we have list human numbers for conduction - these will be faster in small animals and longer in large animals). the conduction of impulse to AV node area is rapid, but then there is slower conduction across transitional fibers and AV node which are poor conductors. b/w atria and ventricles is a ring of fibrous CT, so impulses that might be generated adjacent to the node won't jump down to ventricle - blocked by the fibrous tissue, which is a blockage to conduction. scar can also block conduction, btw. so length of time from SA node to AV node is about 0.3 seconds. then there is about a 0.1 second delay. when impulse gets to distal portion of AV bundle, there's another delay before impulse gets to ventricular tissue. how is this seen on EKG? the space b/w P and QRS complex - this is called the P-R interval. in humans, it's about 0.15-.2 seconds maybe. in the horse, it can be up to 0.5 seconds. in a bird, it is much much shorter. so the impulse is conducted down throuh purkinje system to ventricles, causing depolarization of ventricles, which is seen as the QRS complex, which doesn't always have all three parts Q R and S. once impulse is in purkinje system, it propagates rapidly. that system is there to allow synchronous depolarization of ventricular muscle so heart works as a pump. conduction blocks in this system can cause slow propagation of depolarization, making heart mechanically inefficient, reducing stroke volume. so far, so good. go to single AP that would be generated by a for instance ventricular muscle cell. this cell has no automaticity - it has to be excited by another cell. normally an adjacent cardiac cell. when excited, fast sodium channels open, sodium leaks in - when it gets to threshold potential (about +30) there is rapid opening of sodium channels and rapid depolarization (inside of membrane now becomes positive) due to changes in ionic currents - calcium and potassium currents - and at some point, cell repolarizes - if a whole group of cells depolarize at the same time, you get a QRS on the EKG - during the fast sodium current. then as cells repolarize you get the T wave. notice QRS is shorter than Twave. depolarization is rapid, repolarization is slower. there are changes in intervals - until cell repolarizes, it is refractory to further stimulation. there is an absolute refractory period during the AP, then a relative refractory period and then an excitable period, then a normal resting state. during the T wave, some of the cells are excitable. impulses that occur during the T wave may be able to generate some odd repetitive rhythms b/c some tissue is excitable, some isn't, currnet may flow in odd ways- this is the vulnerable period of EKG, where stimulus could create nasty rhythm disturbance. why does this happen? some cells do not sit at stable resting membrane potential during diastole. their membranes may leak. sodium may leak in, K+ may leak out, less and less, causing slow depolarization. mechanisms differ b/w SA node and other automatic mechanisms. the chapters may not be up to date on htis. you don't have to know what ionic gradients cause this. but anyway the membranes leak. slowly depolarize up to threshold potential, the ionic gates - slower sodium and calcium channels - open. these are the automatic cells that initiate impulses. again - you have ventricular muscle sitting at resting potential waiting for impulse, and you have automatic cells undergoing spontaneous depolarization, driving the cells at resting membrane potential to depolarize. slide: there is an AP from a single cell (recorded intracellularly - not seen on EKG). when there are many of those you see a surface EKG. the mechanical response is during the plateau phase of AP, probably due to an inward calcium current which causes increased release of calcium in the cell,activating contractile machinery. so, the AP in the SA node is pointy. the AP in atrial muscle looks like ventricular muscle but shorter plateau other cells in heart demonstrate automaticity - under normal circumstances they do not drive the heart, because SA node is faster, and because conduction out of the SA node is really good, so if conduction slows or fails from SA node due to electrolyte imbalance, change in autonomic tone, other injury, that impulse may not go fast enough to overcome ectopic pacemaker activity purkinje fiber SP is broader than ventricular AP if ventricular muscle is injured by anything that disrupts the membrane potential, normally quiescent cells may change to ectopic pacemaker foci. if you know all this, dr klein apologizes but we need to go over it. genesis of arrhythmias: automaticity excitability conduction velocity has to do with abnormal changes, or local changes, in automaticity, excitability and conduction velocity. change in automaticity is a change in rate of diastolic depolarization - phase IV depolarization - if it speeds up, you get a rapid rhythm, if it slows, you get a slower rhythm. ACH or vagal stimulation can slow sinus node depolarization. there is less vagal influence on purkinje fibers - so you may see other latent pacemakers expressing themselves. also, maximum diastolic potential - if it resting potential gets closer to it, it may reach threshold faster, but if it hasn't repolarized sufficiently, AP may be weak and not propagate. initiation of impulses pacemaker cells, latent pacemaker cells, non automatic cells conduction - influenced by fibrosis, inflammation, amplitude of AP, excitablity of adjacent cells. ectopic foci can cause tachyarrhythmias. also there is something called re-entry. re-entrant rhythms are quite common. they are explained because somewhere in normal conduction pathway is a block in conduction - due to injury, hypoxia, electrolyte problem, whatever, and so impulse travels through a circuit of atrial or ventricular muscle, depolarizing in the normal fashion that part of myocardium, then propagates backwards through cells that didn't depolarize previously due to that conduction block. when AP gets back to original area, cells are excitable again so you set up a circle here. sometimes it happens just once (bigeminal rhythm) or it can happen over and over. can look like ectopic foci but really just conduction disturbance. what do you do? speed up conduction? slow down conduction? may be important to distinguish b/w reentrant rhythm and ectopic focus tachyarrhythmias: many causes. anxiety hypercarbia hypoxemia pain sensory nerves CNS dz, injury these cause increased sympathetic outflow. think of animal having a fight, being in stress situation, being anxious - these animals are more subject to catecholamine induced arrhythmias. so a cat in the hospital trying to get you and you have to grab it and give it ketamine, realize this animal is at risk for cardiac arrhythmias, compared to a calm cat. hypercarbia and hypoxemia both stimulate sympathetic tone pain during surgery causes sympathetic stimulation touching sensory nerves causes sympathetic stimulation CNS dz may cause catecholamine release you get an increase in automaticity of automatic cells all over the heart. you might get ischemic areas associated with this. if you give beta adrenergic agents you are causing a direct effect on automaticity and conduction velocity. dopamine can generate arrhythmias. cocaine isn't used medically anymore but was used in facial and nasal surgery for anestheisa nd vasoconstricion - interferes with something reuptake and promotes arrhythmias succinylcholine activates sympathetic ganglia caffeine and aminsomething also do something some tachyarrhythmogenic dz states: hyperthyroidism pheochromocytoma (secretes norepi) GDV/torsion (enhanced sympathetic tone) animals with known hyperthyroidism and pheo may be put on antiarrhythmics preoperatively to prevent problems. HBC - cardiac contusion- arrhythmias may be serious - may occur when you try to anesthetise dog to fix fracture sudden K+ rise - to very high levels - can cause v-fib. perhaps from giving stored blood, perhaps from muscle damage eg in malignant hyperthermia, or perhaps when there has been denervation or massive crushing injury to many muscles, the receptors normally only on the NMJ will proliferate (the ACH receptors) over the whole muscle membrane - so when muscle cell depolarizes, there isa sudden efflux of K+ and giving succinylcholine can cause massive opening of all these channels =- a problem in people who get succ during intubation. also when you give too much K+ rapidly eg in penicillin. alkalosis hypokalemia drugs that cause tachyarrhythmias: halothane - catecholamine induced arrhythmias nitrous oxide (enhances symp tone) thiobarbiturates in dogs xylazine - catecholamine induced arrhythmias catecholamine arrhythmias are studied in animals that are awake and are given repeated boluses of epi or continuous infusion repeated until EKG shows repetitive ventricular activity. then dose is recorded. 6 mg/kg were required in control state then, xylazine was given, and that decreased the dose of epi required to cause arrhythmia. ketamine reduced it further. xylazine plus ketamine didn't worsen the problem beyond ketamine alone. but you need to know, that giving epi may cause arrhythmias if ketamine or xylazine have been given. the arrhythmogenic dose of epi is maybe lowered a little by isoflurane, not mcuh, but is very lowered by halothane, which greatly enhances the propensity for catecholamine induced arrhythmias. bradyarrhythmias: xylazine opiates in dogs cholinesterase inhibitors low dose atropine (very low) succinylcholine volatile inhalants methoxamine, phenylephrine, dobutamine, dopamine(horse) vagal stimulation - eye, pharynx, neck, bladder, ovary, adrenal, joint capsule stimulation may all produce vagal reflex response. in fact one way to try to slow a rapid HR is to press on the eyeballs. also carotid sinus pressure may be used in an attempt to slow a rapid HR. but eye stimulation can also cause oculocardiac reflex and stop the heart - important in ocular surgery. usually atropine can prevent these reflexes - or block of nerves from local sensory nerve to vagus, stopping the reflex arc. in marine mammals, they may develop a dive reflex during anesthesia, causing serious bradyarrhythmias - at least, in walruses. intrinsic heart dz - degeneration of sinoatrial node "sick sinus" so there are few impulses being generated CNS dz electrolyte imbalance (increased K+) hypothermia extreme terror - we usually think of fight or flight rxn, but there have been some really horrible studies done in rats who were put in a tank of water and forced to swim until they got tired, and their heart rates slowed drastically, and they were pulled out, and then they learned they woudl be saved, so next time, they didn't have the slow heart rate, because they knew they weren't going to die (uh, yeah, sure...) when should an arrhythmia be treated? is it becoming worse will it affect CO will it affect coronary perfusion? when you see a sinus arrhythmia in a dog, that occurs with respiration, HR may be a little slow, but not that slow, and CO probably not affected adversely especially if dogg isn't running around. when you see an arrhythmia as in this deeply anesthetized pony, where there is a total loss of any rhythm for up to 11 seconds at a time, this is affecting cardiac output. we know it can take about 8 seconds in a horse that is standing up for the brain to be affected by asystole. we know that there is little cerebral perfusion and little coronary perfusion during asystole. if you don't correct this quickly, you will get really bad arrhythmias due to myocardial hypoxia. this animal responded to turning off anesthetic. anticholinergics didn't help. ephedrine helped. slide: atrial ventricular dissociation in horse. we see pwaves which are not preceding the QRS complexes. the ventricular complexes are of AV junctional origin. there is a problem here. the ventricles can fill w/o the atria, but for an animal with other concurrent heart problems, you might be concerned that CO is affected. ----end----