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anesth
4/20
Ewing

the two lectures today have nothing to do 
with each other.
first,we'll discuss the signs of anesthesia and what if 
you misinterpret them?
second, we'll discuss epidural analgesia

why are 
we using all these hoses and bags and so forth
Dr E remarks that our 
class seems unusually lively. perhaps because she called Omar the 
"presidente"

Goals of general anesthesia
we want to acheive a state of 
unconsciousness with no response to or perception of noxious stimuli. 
either an animal is anesthetized or not. anesthesia is a controllable, 
reversible state which involves suppression of muscular, and ANS 
activity.

anesthesia may be light or deep - but we already know that 
anesthesia is an off or on phenomenon, so that is kind of weird. 

we 
hope general anesthesia is reversible and controllable. suppression of 
muscular and ANS activity are separate from anesthesia, but generally 
accompany it.

there is a chart in the handout - "Depth - clinically 
relevant" 

as you go left to right on chart, things get harder to get 
rid of. somatic response to pain is easy to wipe out. a little harder to 
get rid of movement. still harder to get rid of autonomic function - 
breathing can be wiped out by muscle relaxants used on humans during 
abdominal surgery. other autonomic things, as you apply more and more 
anesthetic, hemodynamic responsees (BP, HR), sudomotor responses 
(sweating), or hormonal responses (stress response) may be wiped out. so 
you may give enough anesthetic that there is no BP change in response to 
stimulus, but there is still sweating. hardest to get rid of is the 
stress resposne.

left to right: pain, movement (both somatic), BP/HR, 
sweating, stress response(autonomic)

anesthetic depth: the undefinable - 
dr klide.
there is no unifying definition. there are two types of 
theories - purists have one kidn of thinking, and others think anesthesia 
is a multisite phenomenon based on agent specific actions on 
lipids,membranes, receptors, etc. see handout on anesthetic depth. 
another reason there is no definition is because of the huge number of 
drugs used. often we use inhalants, opioids, and IV agents plus local 
agents. these all exhibit dose/response relationships. sometimes all or 
none, or can be continuous. complications occur. other patient specific 
factors play a role - age, disease, temperature, individual variation. 
depth of anesthesia is a pharmacodynamic event. 
relation b/w dose and 
plasma concentration is pharmacokinetic. 
relation b/w plasma 
concentration and patient response is pharmacodynamic.
generally, the 
higher the dose, the more of an effect it has.

clinically relevant 
effects:
decreased afferent input - we want this (loss of consciousness 
is part of this)
decreased efferent input - loss of motor, autonomic 
responses - we want some of this.
decrased cardiovascular, respiratory 
and GI function commonly occurs, some of which is good and some of which 
sucks. apnea and cardiac arrest are bad extremes.

we want to 
predict/avoid negative outcomes while providing benefits. 

concepts of 
anesthetic depth (the undefinable)

clinical use of term accounts for 
diversity of effects adn clinical needs.
scientific uses of the term - 
applies to lab situations only, where stimulus is possibly realistic but 
single, predictable, evoking specific repeatable response. MAC is defined 
this way.
pain threshold studies are another threshold experiment, but 
patients are usually awake to say "cut that out." scientific definitions 
are required for us to figure out how things work but not good clinically 
b/c we use multiple agents by multiple routes, IV, IM, transmucosal, 
transdermal. patient factors and species differences all limit scientific 
definitions in clinical settings.

you may understand how to anesthetize 
a horse well, but not a ruminant. so there is art and science to this.


before we had such diversity and used mainly ether, Guedel in 1937 
created this scheme: this is also applicable to other inhalants, some 
injectables. movement isn't a great clinical predictor to use to assess 
anesthesia. there is more interest in using ocular and cardiopulmonary 
signs which are useful in most spp. 

unidirectional scheme of anesthetic 
depth (Guedel's scheme)
stage I - voluntary excitement
stage II: 
involuntary excitement
stage III: surgical anesthesia
stage IV: medullary 
paralysis

I: subjective in humans, not well defined in animals. humans 
start getting disoriented while they have some degree of analgesia. 
conscious, but disoriented. ends with unconsciousness. pupils are normal 
in every way. reduced senses. 

II involuntary excitment - starts with 
loss of consciousness, marked by delirium, loss of coordination, 
movement, struggling, vocalizing, intact laryngeal reflexes, nystagmus 
(important in horses), chewing,s wallowing in ruminants, vomition may 
occur in dogs/cats, also irregular respiration, breath holding.

stage 
III: surgical anesthesia - depression of reflexes

plane one: struggling 
stops, light anesthsia, larynx is variably reactive, pupils constricted 
but responsive. eye rotates to species specific eccentric position, 
nystagmus and lacrimation present, regular respiration with ic muscles 
and diaphragm, may be responsive to noxious stimuli. jaw tone 
differentially present in cats, small carnivores.

plane two: moderate 
anesthesia: eyes stay eccentric except with some agents like metofane. 
respiration shallow, intercostals check out before diaphragm, HR, BP 
maintained, variable abbdominal relaxation, marked in cats. 
lacrimation/salivation tail off. still autonomic responses to noxious 
stimuli

plane three: deep anesthesia,. rarely required. fixed central 
eye, pupil dilated and moderate. intercostals lag behind diaphragm, abd 
muscles relaxed. loss of most reflexes except vagal which is hard to wipe 
out. 

plane four: overdose: dilated, unresponsive, central pupil. 
diaphgragmatic shallow breathing, tracheal tug, cardiovascular depression 
is severe, ends in apnea. 

stage IV: moribund. avoid at all costs. 
danger will robinson, danger. apnea is first sign, then circulatory 
collapse and cardiac arrest occur. then animal is no longer anesthetized, 
it is dead.

assessment of depth:

EEG - spontaneous 
electroencephalogram.  summed up meausre of what is going on.
surface 
phenomenon paced by thalamic nuclei. there are correlates relative to 
depth of anesthesia. cerebral blood flow correlates with EEG. when 
patient is unresponsive you can get info about cerebral function wtih 
EEG. patient side monitoring is now possible- EEG machines are no longer 
humongous behemoths. however new equipment is expensive and 
interpretation is difficult. bispectral EEG analysis is one of the new 
ways this is going. noninvasive, continuous. helpful for us? dunno yet. 

Evoked responses - stimulate patient and look for electrophysiologic 
response. usually a nerve, sometimes sound - looks at functional pathway 
integrity. mostly these are used for nonanesthetized patients. deaf 
dalmations are tested this way, electroretinograms are used too. auditory 
clicks so far are best correlated with anesthetic depths, visual light 
flashes also used. nnot sure of application to vet med.
lower esophageal 
contractility - used in humans b/c reticular formation innervates lower 
third of esophagus - probably not applicable to vet med, very agent 
specific.

cataleptic anesthesia: not like above. not unidirectional 
"give a little, give more, oops, dead" type.

ketamine, teletamine, 
phencyclidine (no longer available at all)
these are the dissociative 
anesthetics - humans will report that they feel things but it doesn't 
bother them at all.
induce a cataleptoid state - a physical state of eyes 
open, slow nystagmus, wakeful but noncommunicative, some hypertonus, some 
purposeful movement occurs but has nothing to do with stimulation, there 
is forgetfulness,a nd surface analgesia (not visceral). may be marked 
emergence delirium. nightmares may occur for some time.
dissociatives are 
NMDA receptor antagonists - they bind the PCP site in the ion chnanel 
there, mediating many things (see handout). 
unlike traditional 
anesthetics, these drugs cause marked CNS activation and a lot of EEG 
activity is seen. you have to get over the idea of CNS depression. loss 
of righting reflex isn't equivalent to anesthesia with these drugs. 
patient may be aware but immobile

fig three in notes: multidirectional 
anesthetic depth:

stage I: excitement, disorientation
stage IIa: 
intermittent hallucinations
stage IIb: continuous and more intense - 
useful stage
stage IIC: cataleptoid (myoclonus) - useful - loss of 
righting reflex - may progress to tonic clonic seizures which would be 
bad
stage III: progressive EEG depression - useful stage
stage IV: flat 
EEG (isoelectric) - bad. not useful.

complications - this isn't an easy 
topic to get hold of. 
diversity! species, drugs, circumstances, body 
part, combinations of drugs, there is no single method! don't give up 
though. 
as neurophysiology evolves and toys get fancier and we 
understand more on a molecular level, we get more useful monitoring 
techniques. we think about the brain but the cord is also very involved. 
state of anesthesia is not all supraspinal! many sites in neuraxis are 
involved, there is a lot of agent and site specificity to this. there is 
no single mechanism to explain depth of anesthesia but there are some 
things that we can use.

"in the slow float of differing light and deep, 
No! there is nothing! in the whole and all, nothing that's quite your 
own. yet this is you." - Ezra Pound


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epidural analgesia


this is a great topic.
epidural analgesia is the lecture where you start 
to wonder when you get to touch an actual animal instead of sitting in 
this lecture hall. this is about relief of pain and suffering. 

the 
techniques used are easy. piece of cake. fun to do. the details on what 
goes where and how long it lasts kind of follow in the third year 
elective so don't worry about that now. the theory behind this is very 
complicated. probably out at NBC you'll see - it takes years to get a 
surgery faculty to trust you enough to try these things. one bad 
experience sets the whole thing back, the theory has to be understood, 
you need a missionary to explain it and convert people over.

EA as 
currently done provides partial or complete sensory loss to various 
structures, usually caudal to the umbilicus but not always.

EAs may be 
given as single dose, multiple dose, or continuous infusion (usually by 
catheter which is easy to put in, cheap, and safe. EA can be an adjunct 
to GA, or may replace GA. it's not either or all the time. EA may be 
indicated to control things unrelated to surgery - pain, lymphangitis for 
example - soft tissue inflammation of hind legs causing severe pain in a 
horse. last week they had a hereford heifer that aborted and got cystitis 
- a cow that starts straining will die or turn her whole body inside out. 
she everted her bladder into her urethra, tore her perineum, everted part 
of her rectum,was really broken down. she kept straining. surgical 
correction didn't stop her from straining, so dr donawick asked her to 
look at it. mid-administration of the epidural, she stopped straining and 
was better. 

there is mythology about epidural techniques, esp about 
morphine in large animals. it needs to be broken down. 

techniques - an 
epidural catheter cna be placed in the field, safely and cost 
effectively. these things are all cost effective, easy to learn. and 
really cool - it may be the best quality, longest lasting pain control 
there is. one or more agents may be placed in epidural space at various 
locations.

here is the catch- to make informed and effective choices you 
have to understand your ologies. neuroanatomy and physiology, 
pharmacology, species variability, potential complication. 


history:


first EA used was cocaine in 1900. many early researchers ruined their 
lives with this.
1905- procaine
1940s - lidocaine
1950s - mepivicaine

1960s- bupivicaine aka Marcaine
1970s- opioid and alpha2 receptors

the 
amide type is most commonly used - bupivicaine
new drug - neuropin, 
ropivicaine - different type - lots of promise.

another landmark 
discovery - in mid 70s, they found opioid and alpha2 receptors in the 
dorsal horn of the spinal cord. really revolutionized theories of pain 
processing. this led to clinical use of epidural use of opioids and 
alpha2 agents.

epidural = peridural = extradural --> your drug is 
outside, on top of, the dura mater of spinal column
an epidural can be 
cranial or caudal to the sacrum, and is called
cranial or caudal
spinal = 
subarachnoid = intrathecal --> "true spinal"
this means your drug is in 
the CSF, beneath the arachnoid mater. when you read anesthesia texts, you 
will see the term "spinal anesthesia" sometimes used to refer to both 
types of analgesic techniques.

most often, in large animals, injection 
is made caudal to the sacrum, sacrococcygeal or intracoccygeal depending 
on age and spp. we're doing more catheters at lumbosacral space now, 
though. this is the traditional way though - caudal to sacrum. in small 
animals, commonest spot is lumbosacral space. 

anatomic structures in 
handout - check it out. review them. 
slide: cross section of spine. the 
ligamentum flavum/interarcuate ligament ends at the space - going through 
it may produce a pop. then you are in epidural space - which isn't really 
a space, because there is fat, blood vessels, and stuff in there. may be 
negative pressure, atmospheric pressure, or positive pressure in there. 
beneath that is arachnoid mater and dura. CSF is beneath that, then there 
is the pia mater, then cord. where dura wraps around - they call it 
"dural cuffs" - there is facilitated diffusion of local anesthetics 
there. 

if you remember - you have afferent sensory nerves coming in 
dorsal horn, motor and autonomic fibers from ventral horn; in TL spine 
you have sympathetic ganglia alongside - autonomic component is added 
into spinal nerves here. 

termination of cord:
dogs: L6-L7 (dural sac 
L7-S2)
cats: one segment caudal
LA spp: mid sacrum

at lumbosacral space, 
there is no cord in dogs. you put your needle in there and it can't hit 
the cord. in cats, you can. in puppies, you can too.

in large animals, 
the cord ends under the sacrum. that makes it easier to remember, and 
means you are not over cauda equina at the lumbosacral space. this is why 
they often go caudal to the sacrum. 

choice of injection site: base this 
on area of intended blockade, what your agent is, how good your restraint 
is, and if you are using a catheter.
in large animals we are often trying 
to desensitize perineum, external genitalia, part of vagina, and tail. 
used in urogenital surgery etc - doesn't affect legs. 

in pigs, small 
ruminants - can do more of a blockade like in small animals, blocking 
everything caudal to L1. 

also agent specificity- pharmacology of the 
agent is a factor.
if you don't have good restraint, do not do this!
if 
patient is standing, recumbent, awake, sedated - think about these 
factors too. also consider if placing catheter or doing direct injection.


gnerally, you want to preserve motor function in large animals at all 
costs. horses freak out of they have limb weakness without sedation. 
adult cows may be ok if in recumbency but still this isn't advisable. if 
they go down, they fall ungracefully, break bones, etc. avoid. small 
ruminants can be managed better with loss of motor function.

cranial 
distribution, "spread ahead" of local anesthetics causes loss of motor 
function. opioids and alpha2 agents don't do this - they spare motor 
function.

injection site is generally caudal to sacrum regardles sof 
type of drug, usually only affects sacral nerves, this site is less 
risky- and the exception is pigs - lumbosacral is the only option in pigs 


pharmacology - 
local anesthetics- 
inhibition of inward sodium current. 
inhibition of other ion currents. interaction with adenylate cyclase, 2nd 
messengers, phospholipases, etc. tissue and neuron specific. we do not 
know how exactly they interact with sodium channels. 

go back to that 
diagram - if you do a lumbosacral injection of local anesth in a cat, and 
it falls down, because you have blocked motor fibers to hind legs - do 
not forget about autonomic components you have also wiped out - things 
like blood vessel innervation. if you do this and you give too much drug 
or give it too fast, and you wipe out enough of these sympathetic things, 
you can wipe out vascular tone. splanchnic circulation can vasodilate and 
whole blood volume can go in there. you cause cardiovascular collapse, 
total loss of venous return. s if you give too much too quickly of 
lidocaine into lumbosacral space, you will cause this. if you give it too 
far cranially, in the Cspine, you can compromise intercostal function, 
but that isn't going to happen here. cardiovascular collapse is more 
dangerous here.

remember that.

fiber size and function - spinal nerves


a fibers are somatic nerves.
a alpha are big, fast, motor nerves thick, 
heavily myelinated
a betas are muscle, touch, pressure receptors
a gamma 
- muscle spindle receptors - tiny tiny
a delta - pain, temperature- very 
thin myelinated fibers - amenable to rapid blockade

b fibers are 
preganglionic autonomic - vasc sm musc
c fibers - pain fibers, 
temperature. these are teeny tiny tiny fibers, easy to block.

with 
locals epidurally or spinally you can differentially block these, you can 
give such a weak solution that you block only pain and not motor fibers 
but it is very hard. in large animals, when you do this, assume motor 
blockade will occur if you are blocking spinal nerves, and prepare for 
it. if you give a local do not count on muscular control.

minimal 
blocking concentration Cm - lowest concentration that will block a nerve 
in a given time in vitro
this compares relative potency of local 
anesthetics. tissue conditions influence this in vivo, also fiber 
diameter, activity. pH, temperature, ion concentrations, fibrous tissue 
barriers. 

Cm is related to how rapidly fiber normally fires, too - 
those that fire more slowly are harder to block.

tachyphylaxis- in 
theory, this means drug tolerance. basically, this is when a drug has 
declining effectiveness b/c it is given repeatedly - as with opiates,drug 
addicts. local anesthetics, if you ahve a catheter in place and you do 
not dose at the right intervals - if you wait too long - you end up using 
too much, just know that tachyphylaxis occurs, declining effectiveness if 
not timed right. so then you give more. that's ok. duration, field, 
potency all decrease, and top-ups end up being larger instead of smaller 
as they usually are.

potency, onset, duration - important
lidocaine 2%, 
mepivacaine 2% - onset 10min, duration 45-90 min or mepivicaine up to 120 
min. comparable potency, toxicity

bupivicaine- slower onset 15-20 min, 
but lasts longer, 4 to 5 hrs, more potent and 3-4x more toxic. usually 
0.5% so you use the same #mL

physicochemical properties also important- 
lipid solubility, protein binding, etc. 

non pharmacologic factors -some 
locals cause vasodilation, some cause vasoconstriction. this may 
influence potency, onset, duration. dosage - an interesting property 
where mass (mg) of drug and volume of drug are important - if you have 2 
ml of .2% solun vs 10 ml of .2% solun, your bigger dose goes further 
cranially. but, if you take 2 ml of .2% solu'n, and 2 ml of 1% solun, the 
stronger solution also goes further forward. so concentration and volume 
are important wrt cranial migration.

another factor to mention - 
epinephrine is sometimes added into lidocaine. you don't need to add it 
though.
site of administration - epidural/spinal. influences things too. 
spinals have faster onset, shorter duration. we never plan to do a 
spinal. 

toxicity: cardiovascular
-=bradycardia
-ventricular 
dysrhythmias
-wide QRS due to slowed conduction
-negative inotropic 
effects with longer acting agents - this is why ropivicaine was 
developed, b/c bupivicaine can be really toxic - has killed people.

this 
isn't the first system to show toxicity but anyway, these are the effects 
you can see.

CNS is first system to be affected. 
-lightheadedness is 
reported in human volunteers
-sedation/drowsiness follows, then, 
unconsciousness, seizures (inhibitory pathways are knocked out, causing 
seizures - tremors of face/limb may precede tonic/clonic siezures) coma

-neurotoxicity parallels potency - bupivicaine is worst
-prevention - 
know convulsive threshold - 10 mg/kg in mammals. max safe dose by all non 
IV means combined therefore is 8 mg/kg. llamas - lower. 
-tx: do non 
pharmacologic things first - airway, breathing, circulation. then 
postural changes to support blood flow to head. identify, treat 
hypotension and dysrhythmias - siezures. use drugs to control siezures, 
pressure, etc. do not give pentobarb.
-preservatives should be avoided. 
single use vials are best. agents like sodium metabisulfite or 
formaldehyde may be present. these are not good. parabens are present in 
many drugs and these can cause allergic reaction. ideally use additive 
free drugs.

so IV lidocaine infusions are used in horses and can cause 
sedation (tx laminities)

opioids and alpha 2 agonists - different. 
bind 
specific receptors, can be specifically antagonized. 
always provide 
differential blockade.
duration is longer, onset is slower
cranial 
migration

when you inject a drug, it can go a bunch of places. you need 
it to get into the CSF. most drugs never cross the dura at all - it gets 
systemically absorbed or leaks out - a tiny bit crosses the dura - that 
is the important amount.
once it is in CSF bathing spinal cord, activity 
depends on how water soluble it is. morphine, very water soluble, will 
sit in CSF, and migrate forward toward brain- produce extensive 
multisegmental block - morphine notorious for being long lasting - in 
humans, 18-24 hrs. in small animals about as long. in hereford - lasted 
22 hrs. fentanyl, oxymorphone, very lipid soluble, won't sit in CSF, 
rather diffuses into lipid of spinal cord - stays where you put it - 
produce segmental block. 

note: dura is fibrous, not lipid. driving 
force across it is determined by molecular size/shape, not solubility.


informed drug choice depends on waht you want to block, what drugs will 
get there, if it shoudl be localized, etc. onset time of alpha2 is 
slower, over 20 min or even over 30 min. lasts realy long. unlike locals 
cranial migration theoretically only produces pain sense blockade - not 
motor blockade. locals wipe out everything, these only wipe out pain. 
remember that.
sadly, i have to go to my grandma's birthday party now, 
because it is 4:51. seeya.
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