---start--- anesth 4/13 perkowski so, today and tomorrow we will discuss anesthesia and the cardiovascular system. this is confusing and you will probably wonder what it is all about but hang in there and perhaps things will become clear eventually. first, we will have an overview of the sympathetic NS and cardiovascular system. use the stuff you learned from Dr. Knight (ahem) and build on that. ok. first, you should know about blood pressure. there are some words we use when we talk blood pressure - we talk about pulse pressure, which is what you palpate when you palpate a pulse - this is the difference b/w systolic and diastolic pressure. you can have small or large pulse pressures, but still have the same mean pressure. another thing to remember is that mean pressures are not half way b/w systolic and diastolic pressure. remember your heart doesn't spend half the time in systole. only 1/3 of the time is in systole, and 2/3 in diastole. so mean pressure is always a bit closer to diastolic pressure, though as HR increases, your time in diastole falls, and mean pressure gets closer to the midpoint. again, you can have changes in mean pressure without changes in pulse pressure. this is difficult. palpation of pulse isn't the best way to assess blood pressure. talking about blood pressure, hypotension -what are we really worrying about? normal mean pressures are 80-120 mmHg - we want to stay within 20% of that under anesthesia. we draw a line at 60 mmHg because the renal vascular bed, coronary and cerebral vascular beds all autoregulate their blood flow to maintain pressure b/w 50-60 and 150-160 mmHg. so we want to stay off the knee of the curve. if you go below 60 mmHg, you compromise flow to kidney, brain, etc. another thing in large animals is peripheral myopathy/neuropathy. the anesthetized horse is placed on a number of pads - is prone to peripheral myopathy/neuropathy - so we try to maintain pressure >60 mmHg to prevent these problems. pressure at 60 mmHg for an hour or more can result in myopathy/neuropathy so you really need to keep it higher than that. hypotension: cases: blood pressure = CO x systemic vascular resistance. CO = SV x HR SV = venous return (preload) and contractility now, remember - there are coupling factors - preload and afterload. as systemic vascular resistance goes up, afterload may go up, making it harder to pump, and SV and CO may go down. also, as HR goes up, CO goes up to a point, but if HR goes up too much, there is reduced venous return and a reduction in SV. venous return can also affect contractility - remember, as your fiber length increases as heart fills, the force increases - the more the heart is filled up, the stronger the contraction - until you overdistend, and ability to contract starts to fall. all these things are interrelated. EKG of 5 yr old great dane, FS. this EKG was taken during a GDV episode. we see cardiac arrhythmia - ventricular tachycardia? and some normal sinus rhythm. there are nice pulse waves after each beat. during the ventricular arrhythmia, the pulse waves are only about 1/2 as big as during sinus rhythm. also, when two ventricular complexes occur right next to each other, there is a pulse deficit after the second beat. maintenance of BP: how does the body maintain BP? normally, one of three mechanisms is used. manipulation of autonomic NS, manipulation of humoral mechanisms (vasopressin or renin/at/aldosterone) or local control (vasoaction). anesthesia can blunt all three of these responses. local control and baroreceptor reflexes are more important in early hypotension. humoral mechanisms kick in after hours/days. so we will focus on how anesthesia influences sympathetic and parasympathetic nervous systems. parasympathetic: also called the cholinergic NS: arises from craniosacral portions of CNS ACH is the mediator, and ACHesterases break down ACH in the synapse or plasma. we're talking mainly about the vagus nerve, CN X, which goes to heart. two types of receptors - nicotinic and muscarinic. nicotinic are in all autonomic ganglia, symp and parasymp and adrenal medulla and NMJ. muscarinic recptors are in postganglionic sites in heart, smooth muscle, and glands. so giving anticholinergics like atropine blocks these muscarinic postganglionic receptors. cardioascular effects of PSNS: mediated mainly by vagus with influence on SA and AV node. primary thing it does is decrease HR by decreasing conduction through SA node, and decreasing AV conduction. there are minor effects on vascular tone. sympathetic NS aka adrenergic NS - thoracolumbar part. primary NT is norepi which is removed by reuptake or broken down by MAO, COMT. norepi isn't the only NT. ACH is also involved at ganglia, the adrenal medulla makes norepi and epi, ACH is released from sweat glands in some spp, serotonin, neuropeptide Y, ATP, and dopamine are also involved. effects on heart - SNS opposite vagal effects - increase HR. act on SA node and AV node - increase HR, increase AV conduction. norepi is released, can affect heart through B1 receptors. the beta1 receptors are key to increase HR and contractility. epinephrine from adrenal medulla circulates and also increases HR and contractility by binding B1 receptors in heart. sympathetic NS also has effects on vasculature: creates normal sympathetic resting tone. can bind alpha 1 or alpha 2 receptors and cause vasoconstriction, or B2 receptors and cause vasodilation. norepi effects are on a1 and a2 receptors and act to maintain systemic BP, create normal sympathetic tone, control distribution of blood flow. there are also a2 receptors found presynaptically. norepi can bind there to inhibit further norepi release. the presynaptic a2 receptors can limit vasoconstriction. also in CNS cause some sedation by decreasing norepi release, and decrease sympathetic outflow to places like the heart. so a2 agonists have serious cardiovascular effects. another point is that norepi doesn't bind beta2 receptors. epinephrine binds b2 receptors on bronchial smooth muscle and some vascular beds - skeletal muscle,heart. when you stimulate b2, you get bronchodilation and vasodilation. stimulation of B1 receptors on the heart by epi or norepi increases contractility, automaticity, and conduction. so the differential binding of B2 receptors is important. there are also some b2 receptors in heart,not usually important - until heart is diseased,and then b1 receptors aren't visible on cell surfaces anymore, and you have to try to modulate activity with b2 receptors then. dopamine - DA1 receptors - vasodilation of renal,mesenteric,coronary beds presynaptic DA2 receptors - inhibit NE release, probably important in CNS. also dopamine is a precursor of NE, E. effects of anesthesia on SNS: there is a generalized decrease in sympathetic tone with all anesthetic agents, just by virtue of the fact that the patient is sleeping. normally, we keep a balance b/w sympathetic and parasympathetic tone in the heart. now, you decrease sympathetic tone by putting animal into sleep state - CO will fall, vascular tone is going to fall, patient gets a bit vasodilated. this is just due to sleep. not anything else. specific drug effects: many drugs have SNS effects, for example: phenothiazines eg acepromazine droperidol those types are alpha agonists, they create peripheral dilation opioids - generally nice to cardiovascular system but they also increase parasympathetic tone, which reduces the HR and CO. easy to fix that, though. also alpha2 agonists - these have postsynaptic and presynaptic effects. what else occurs? remember there are at least three ckinds of peripheral receptors in SNS - baroreceptors, stretch receptors in aortic arch/carotid sinus; mechanoreceptors in heart and pulmonary vessels; chemoreceptors in carotid and aortic bodies. the baroreceptors are most important. the mechanoreceptors cause increased HR as heart gets distended and cause urine volume increase. chemoreceptors mainly deal with respiration and are easily overridden by baroreceptors but can also be synergistic with baroreceptors. baroreceptors are important for minute to minute maintenance of BP - but their function is depressed by the drugs we use, esp inhalants. baroreceptors sense changes in BP, remember, so, at low levels as your pressure goes up, the barorecptor starts to fire. as pressure increases, it fires more and more. so what happens is the carotid sinus and aortic arch baroreceptors send messages to the CNS saying "pressure is going up! do something" and the CNS sends impulses through the vagus to increase vagal tone, decrease HR, and also sends vasodilation messages to the periphery. this also works backwards - as pressure falls, firing decreases, message to CNS "pressure is falling, do something!" so we worry during anesthesia because these things are depressed. angiotensin/aldosterone/vasopressin stuff - anesthetics can influence humoral mechanisms but more important over hours/days really. potent inhalant effects on autoregulation - needed for moment to moment changes in blood flow, used by kidneys, brain, heart. autoregulation occurs b/w 60-160 mmHg. note that as we increase our concentration of potent inhalant, we decrease the ability to autoregulate. now, flow in these vascular beds really depends on what the mean arterial pressure is doing - which is usually falling. esp in patients with brain tumors, we worry a lot about autoregulation esp in brain. cardiovascular depression and hypotension commonly occur in the anesthetized patient. slide: anesthetized capybara. it doesn't matter what drugs you are using or what the patient status is -t his is a common occurence. therefore, examine your patient first and see what you can do to try to help maintain your BP as much as possible. there are species differences here. horse that weighs 1000 lbs vs cow that weighs 1000 lbs - if you anesthetize both, you'll see - ruminants maintain BP much better than horses. dogs maintain much better than cats. rabbits suck. there are also some breed differences. big belgian draft horse vs thoroughbred racehorse, sighthound vs beagle. age is also important. very young and old patients don't handle anesthesia as well. pediatrics: under 12 wks: heart has low contractile mass/gram of tissue, low ventricular compliance, CO very rate dependent since can't increase contractility well. the SNS is also not well developed yet. there is decreased vasomotor tone and increased susceptibility to hypothermia. there are also (as if that was not enough) immature baroreceptor responses. so it is key to maintain HR at a higher level in these little guys. normally when we anesthetize pups/kits we try to maintain pressures in high 50s. very old animals have their own problems: geriatric patients have decrease in ventricular compliance and low COs, with increased incidence of cardiac disease and arrhythmias. also there is decreased elasticity in the vasculature and most importantly a decrease in responsiveness to catecholamines. so when you anesthetize an older patient, it is harder to deal with problems that occur. if you get them too deep and pressure craps out it is hard to retrieve the situation. patient history is important. why did patient come in? emergency? HBC, colic, GDV, sepsis, what? known medical conditions - endocrine, cardiovascular, etc. dog with huge pericardial effusion has extremely reduced venous return and crappy cardiac output - must maintain high HR to maintain CO. cat with hypertrophic cardiomyopathy - the opposite - you have huge, hypertrophied ventricle, coronary arteries can't oxygenate the whole wall, you must not increase the heart rate at all b/c that increases heart's oxygen consumption. you want to decrease HR, optimize diastolic fililng. known meds? Many old patients are on vasodilators or antiarrhythmics. worry about this when anesthetizing the patient! also, now that behavior is a new specialty - dogs come in on tricyclic antidepressants or MAO inhibitors. the tricyclics cause muscarinic blockade (tachycardia), alpha 1 blockade (vasodilation), and inhibition of NE reuptake. so you have to anesthetize it and hope nothing goes wrong. scary. antibiotics too - aminoglycosides can decrease ventricular contractility and vascular tone. other abx may also have effects on BP. it's a big deal to give abx to anesthetized animals - may cause precipitous drops in BP. do good PE. look at cardiovascular system. if patient is bleeding it may be hypovolemic. or, may have non obvious problem causing hypovolemia. you have to assess tissue perfusion, HR, rhythm, and you have to listen to the heart. respiratory system isn't directly associated but if you are very hypoxemic it is hard to maintain vascular tone, if you aren't ventilating well you may increase sympathetic tone and be susceptible to arrhythmias. GI distension can cause arrhythmias or compromised venous return, decrease BP. CNS lesions or high cord lesions can have BP fluctuations, problems with failing compensatory mechanisms. K+, Mg, Ca++, acid/base balance can have real effects on contractility and vascular tone. severe hyperkalemia - seen in animals with urinary problems - high incidence of arrhythmias and cardiac arrest with anesthesia in these situations, b/c the depolarization of the cardiac AP is based on a sodium current which makes the inside of the cell positive, and then the potassium channels open as sodium channels close, and potassium is supposed to rush out to repolarize the membrane. when you are hyperkalemic, extracellular K+ is high, and repolarization occurs to a less negative resting membrane potential - closer to threshold potential - promotes fibrillation. calcium is bad if very low or high. hypocalcemia causes decreased ventricular function, decreased vascular tone; hypercalcemia changes threshold potential, promotes bradyarrhythmias. magnesium is the new, hip, cool electrolyte to worry about. too low: refractory hypokalemia, arrhythmias, hypocalcemia; too high: decreased contractility, vasodilation don't need to remember all that detail acidosis- can cause generalized depression of cellular function of myocardial and vascular smooth muscle cells. respiratory acidosis - increased CO2 - a problem b/c increases sympathetic tone, promotes arrhythmia. causes of hypotension during anesthesia - you're ready to go. now what? ---break-- ok. causes of hypotension during anesthesia: anesthesia/anesthetic agents can affect all the blood pressure maintenance parameters. most commonly, inadequate volume is the cause of hypotension. fluid administration during anesthesia is key. many private practicioners get away with out fluids, but they are still important especially with sick patients. many owners withold water the night before when they take the food away. some patients are more critical than others and may be hypovolemic due to their disease. despite preoperative deficits, there are fluid losses during surgery. 2-4 mg/kg/hr in awake patient during anesthesia there are: greater evaporative losses from respiratory tract greater evaporative losses from exposed body cavities greater third space losses with surgical manipulation so not only are there preop deficits, you have increased ongoing fluid losses. tomorrow we'll talk fluids. if you have fluid deficits, you have decreased venous return. you may have an absolute fluid deficit, or relative fluid deficit- with decreased sympathetic tone, and vasodilation, you need more fluid to fill up the vasculature or you will be relatively hypovolemic. decreased venous return may also occur due to compression of the great veins - pregnant equid in dorsal recumbency, or even just any equid in dorsal recumbency - viscera compress vena cava. so patient position can be really important. after 15 minutes in dorsal recumbency, the central venous pressure drops from about 22 cm H2O to 7 cm H2O. slide: a horse on a ventilator, pressure waves - shows what happens when you give PPV - when you give a breath, the first thing that happens is you increase pressure within the chest and the next heartbeat generates a stronger pulse because you decreased the gradient for blood to flow out. but, you decrease venous return, so then next beat is lower. you see cyclic changes in blood pressure. in hypovolemic patients this can be very pronounced. surgical manipulation with associated pooling or trapping of blood can also influence venous return. myocardial contractility - anesthetic agents - alpha two agonists feed back presynaptically to inhibit NE release - when they do this centrally they decrease sympathetic outflow to heart, decreasing myocardial contractility opioids - nice to cardiovascular system, but demerol or meperidine is different - was originally designed as an anticholinergic. it decreases myocardial contractility. ketamine - normally thought of as a sparing drug for the heart, but you must remember that it is sparing b/c it causes endogenous catecholamine release - the catecholamines cause an increase in HR and contractility - so if you give ketamine to a sick animal you can unmask the direct effects of ketamine - a negative inotropic effect occurs. there can be up to a 50% decrease in mean arterial pressures in a patient who can not mount the endogenous catecholamine release. barbiturates - thiopental is most common induction agent in dogs, also used at NBC - causes some cardiovascular depression and decreased contractility - ok in healthy dogs but can be a problem in sick patients. propofol - the new cool drug - some mild effects on contractility, though. potent inhalants - halothane, enflurane, isoflurane, sevoflurane, *flurane. when you give them at MAC or higher, they decrease BP to below waking pressures. the more you give, the lower the BP goes. why? mechanisms vary. halothane and enflurane are direct myocardial depressants. these will reduce CO on their own. isoflurane maintains CO. or at least, CO doesn't fall on isoflurane. stroke volume falls with isoflurane, but HR increases b/c there isn't much effect on the baroreceptors with iso. isoflurane isn't a myocardial depressant, it decreases BP for other reasons. nitrous is also a myocardial depressant but like ketamine it causes catecholamine release so CO and BP are maintained well. we do not use nitrous here anymore but some places do. myocardial contractility: release of depressant factors - ischemia-reperfusion injury (unwinding gastric torsion), sepsis, pancreatic manipulation can all release factors that depress contractility underlying cardiac disease can also cause reduced contractility anesthetic agents can also affect stroke volume by increasing afterload,making it harder to pump blood out of the heart. classic case - alpha 2 agonists. 1 mg/kg xylazine IV to a dog causes first a big rise in BP, due to the peripheral vasoconstriction caused by peripheral A2 stimulation - then a big decrease in BP due to centrally mediated decrease in sympathetic outflow causing decreased CO, decreased HR, and also the increased SVR/afterload. so there are at least three reasons for decreased BP with a2 agonists. we rarely use a2 agonists except for the occasional cat castration, for teaching purposes. we use xylazine more often in large animals b/c there are fewer other drugs to choose from that work well in horses. horses do not do well with opioids or valium so xylazine looks better. arrhythmias - can affect SV by affecting ventricular filling. thiopental increases automaticity in the heart, so when inducing with thiopental you often see increased HR - but sometimes an arrhythmia develops - here we see a bigeminal rhythm where every normal sinus beat is followed by a VPC. inhalants can also cause arrhythmias - halothane more so than iso. halothane sensitizes the myocardium to catecholamine induced arrhythmias. so if you use halothane and then have HR problems, and you have to give epinephrine, you can have a problem. chance of ventricular arrhythmia is higher. you would probably switch to iso or something. heart rate - increased vagal/parasympathetic tone is caused by many drugs =- the increase is relative to sympathetic tone. opioids increase vagal tone - can see 2nd degree AV block in dogs after opioid administration. horses get excited by opioids so their normal 2nd degree AV block goes away. oy. alpha2 agonists also cause bradycardia and 2nd degree AV block visceral manipulation, entering joint capsules, or doing eye procedures can all cause a vagally mediated bradycardia or even cardiac arrest if no anticholinergic has been administered. remember that most anesthetics decrease baroreceptor responsiveness which reduces ability to maintain BP. potent inhalants are worst - halothane and enflurane cause drops in SV/BP but no increasin HR occurs. in contrast, isoflurane doesn't decrease baroreceptor responsiveness so well. desflurane - very similar to isoflurane enflurane more like halothane CO = SV x HR SV -- venous return, contractility, afterload,arrhythmias HR -- parasymp vs symp tone, baroreceptor response look at CO in dogs on pentobarb and halothane - CO drops 20%. it drops further when dog becomes hypovolemic (decreased venous return), more with increased abdominal pressure (further decreased venous return) - the point is, more than one thing can go on at one time in your patient. now, BP isn't just CO - it's also systemic vascular resistance SVR already SVR is decreased due to decreased symp tone also, histamine release is common in dogs, especially when given opioids, when given atracurium, when mast cell tumors are mucked with. there are some spp/breed predilections. SVR is influenced also by anesthetic agents - phenothiazines vasodilate, reducing SVR guaifenesin - centrally acting muscle relaxant for lg animals - also vasodilates propofol - depresses myocardium a little but mainly is potent vasodilator. of all the drugs we use, it causes more hypotension than about any other agent we use. the dilation is very pronounced on the venous side, which is already holding 70% of your blood. your circulating blood volume therefore goes way down. mms turn "propofol purple" due to venous engorgement. potent inhalants - most people consider iso a lot safer than halothane. most private practicioners choose iso if they only have one agent. but looking at BP at equivalent mac values - presures are lower with isoflurane than with halothane. so why do people say halothane is so much worse? the reason halothane decreases BP is myocardial depression. iso does it from vasodilation. halothane doesn't cause much vasodilation; isoflurane causes a lot. enflurane does both. so, why use iso? it's easier to deal with vasodilation - can give fluids, raise pressure. also, these studies are in normal animals. if animal is septic or has other problems, you have other myocardial depressants on board, and halothane is more dangerous. also, halothane can cause arrhythmias if you have to give epi, etc. other things causing decreases in BP - epidural/spinal anesthesia - frequently you inject a local anesthetic around the spinal canal. how do these work? they block sodium channels. this stops the wave of depolarization. that's why you feel numb. the thing to remember is that sensory fibers aren't the only fibers there. other fibers are also blocked. motor fibers may be blocked - but they are bigger, more resistant fibers, so you can give a sensory block without giving a motor block. but sympathetic fibers are smaller than sensory fibers, so you can't give a sensory block without giving a sympathetic block, causing vasodilation, which can cause huge decrease in BP. so epidurals are contraindicated in hypovolemic patients. SVR - also decreased by beta2 agonists like isoproterenol and epinephrine, and hypoxemia, sepsis, acidosis all decrease vascular tone note: isoproterenol is a beta1 and beta2 agonist - you get big increases in HR with it - don't use it much anymore. with epi, normally alpha1 effects predominate over beta2 effects, but if you gave acepromazine first, you blocked the alpha1 and alpha2 effects, adn now your b2 effects will predominate - they call this epinephrine reversal - can be on board exams. just give more epi. how can we recognize these problems? changes in HR or rhythm. increases in HR are a major response to hypotension but baroreceptors don't work so well under anesth, remember. other causes of tachycardia: inadequate anesthesia - pain hypercarbia (hypoventilation) hypoxemia drugs (anticholinergics, et al) hyperthermia (increased metabolism, increased CO2 production) so, tachycardia, while helpful, isn't the only factor here. tissue perfusion - assess this by looking at mucous membranes. are mms pink, pale, white, injected, moist, tacky, what? is CRT normal? should be <2 sec. skin condition is important for assessing volume status in awake patients. temperature of extremities - with hypovolemia, extremities get cold. mental status - hard to assess under anesthesia but you can look at pupillary reflexes, and urine production. also can palapate peripheral pulses - dorsal metatarsal artery in dog, below hock on medial side. also can palpate femoral pulse. remember you are feeling the difference b/w systolic and diastolic pressures. you have to palpate not just the pulse, but also the artery between pulses. do you feel a hard rigid tube or does the artery disappear? then you can assess mean pressure. a very vasoconstricted patient may have poor pulses, but it will feel similar to a patient with a thready pulse due to poor cardiac output. the pulse pressures in both are low, but mean pressures are very different. also if you can feel a femoral pulse, systolic pressure is at least 60, if you feel dorsal metatarsal it is at least 80, if you can't feel it at all, it's very bad. a lot of private practicioners are using pulseoximetry now, but they use them not to see what is going on with oxygenation (which is what they are for) but to see what is going on with peripheral perfusion (which is not what they are for). they work by flashing out a pulse of red light and then a pulse of infrared light, and measuring the absorption of light at those wavelengths. reduced hemoglobin absorbs more red light than oxygenated Hb, and oxyHb absorbbs more infrared. so the machine figures it out and then looks at absorption and says ok, the artery is pulsing, so some absorption is due to tissues around the artery, some is due to the non pulsatile capillary blood, and some is due to other stuff, but all we care about is what is in the pulsatile arterial blood. so it subtracts out other stuff. this means the pulsox has to sense a pulse in order to work. many private practicioners put the pulsox on and use it to monitor BP - if pulsox isn't working well, your pulses probably suck. if you are on 100% O2, your pulsox should be reading out fine, but if perfusion goes down, the pulsox gives false low readings. people use this for that, but it is suboptimal. what do we do here? AT PENN, WE use other methods. auscultation of korotkoff sounds - like you have done at the doctors - cuff and stethescope with sphygmomanometer method. you blow up cuff, slowly release pressure while listening and when you have flow from proximal part of arm reaching distal part of arm - when arterial blood flow hits the static column - you get turbulence - korotkoff sounds. so when you hear that, that is the systolic pressure. then as you decrease pressure, sound gets larger and larger and then goes away- when it goes away, that's the diastolic pressure. this is cheap and noninvasive, but really is good for systolic pressure only, the accuracy depends on cuff size, it isn't automatic, and it requires training. cuff should be 40% circumference of limb, or will read pressures too high. what we do here is use ultrasonic doppler flow probes - similar concept to the korotkoff method - you blow up a cuff, put your crystal transducer distal to the cuff over an artery. an ultrasound wave goes out and is reflected by blood. the transducer amplifies the signal. so again, you hear the sounds starting with systolic and ending with diastolic pressures.the peak pressure is the mean pressure though you usually can't appreciate that. advantages of doppler - large or small animals - relatively inexpensive, noninvasive, simple, portable - disadvantages - systolic only, accuracy depends on cuf size, not automatic. dinamap machine -used at VHUP a lot. oscillometric device. also uses a cuff - machine blows it up, then decreases pressure incrementally, and as it reaches systolic pressure, the arterial pulse starts to push against a sensor in the cuff and it measures this. it measures systolic, peak/MAP and diastolic pressure. this is again simple, noninvasive, and now automatic. disadvantage - still depends on cuff size, inaccurate with arrhythmias or hypotension, and not sure how well it works in cats or very small patients. ---end----