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isoflurane.

used very 
commonly in human and veterinary anesthesia. most insoluble of commonly 
used inhalants we've discussed. onset/recovery rapid since insoluble. 
effects on cardiovascular system in animals, if used w/other drugs, slows 
HR, if used alone, HR goes up. tends to preserve cardiovascular function. 
at reasonable doses in normal dogs, no change in BP or CO. decreases 
peripheral resistance, and at high doses BP will fall. in horses, dose 
related decrease in pressure and CO. in handout is discussion of study in 
horses with PPV and spontaneous respiration. there was less depression in 
horses with spontaneous respiration - probably b/c w/spontaneous 
breathing, pCO2 will rise, causing sympathetic stimulation, supporting 
cardiovascular function. if you ventilate them, you control pCO2, 
sympathetic response doesn't occur.

only .2% of inhaled gas is 
metabolized in liver. some effect at NMJ, so good relaxation. effects of 
NMblocking agents is enhanced.  iso used for many spp; people working 
with birds like it b/c they think it's safer in birds than halothane was. 
recommended in sick animals of any spp over halothane. 

enflurane was 
popular in humans for a time, but not anymore. different because it 
causes CNS excitement while producing anesthesia. can produce EEG 
patterns reflective of seizures. sometimes that's all you see, sometimes 
you also see motor activity associated with those patterns. the effect 
increases with decreased CO2 or increased depth of anesthesia. also 
causes increases in production of CSF so bad for problems with 
intracranial pressure. might increase O2 demand in brain, and also 
increases cerebral blood flow like all inhaled anesthetics. has the 
biggest effect on cardiovascular function of all these inhaled anesth. 
decreases CO and BP. undesirable effects are twitching, seizures. 
inexperienced people may interpret that as movement and attempt to 
increase the dose of drug, overanesthetizing the animal. it's not used 
here in small animals, maybe in large during surgery course. 

desflurane 
- a newer anesthetic, released a couple of years ago. has been approved. 
main advantage is it has very low solubility. 0.4 = blood:gas solubility 
coefficient, so fastest induction and recovery. vapor pressure very high, 
may be boiling at room temperature. cardio effects - similar to 
isoflurane. 

giving inhaled anesthetics: patients breathe through 
breathing system. most common one contains chemical to remove CO2 from 
exhaled gas, and then patient rebreathes some of previously exhaled gas.


with desflurane and some other drugs, there are interactions with the 
chemical that removes the CO2. if the chemical gets dried out, the 
desflurane and sevoflurane will react. with desflurane, enflurane, and 
isoflurane, if exposed to dried out soda lime, they will react and 
produce CO, with desflurane making the most and iso making the least. 


sevoflurane is also of interest due to low solubility - about 0.6, a bit 
more soluble than desflurane but still very very low. it is metabolized 
some, and inorganic fluoride is released, but clinically the problem with 
metofane isn't seen with sevoflurane. but sevoflurane reacts with dried 
soda lime, to make compounds A, B, and C. compound A can be nephrotoxic. 
studies in rats and people show this, but work hasn't been done in other 
spp yet. so they use this in people but until there's more information 
about this compound A it probably won't be used much in veterinary 
medicine. 

nitrous oxide: N2O - whipped cream, dentist, abuse, 
anesthetic
do not confuse N2O with NO
nitric oxide: NO - pain 
transmission, vasomotor tone (erectile tissue), potent pulmonary 
vasodilator, neurotransmitter

MAC in dog is 188% - you can't acheive MAC 
at atmospheric pressure with N2O. so, it's given at some small fraction 
of MAC. cardiovascular effects in normal individuals - increases BP. 
slightly sympathomimetic. as patients get sick or get other depressant 
drugs, cardio response is less predictable. 

what 
why is it used? other 
properties of N2O - to induce anesthesia with inhaled agent, induction is 
faster if patient breathes more, with a higher minute volume. N2O isn't 
very soluble. bgsc is 3.46, but it's given in high concentrations, so 
amount taken up by the body in first few minutes is quite high. 
therefore, due to rapid uptake, it produces the second gas effect - 
appears as if the animal were ventilating with higher minute volume, 
carrying gas into lungs and speeding induction. ie, if two gases are 
inhaled together, and one is taken up in higher quantity, it causes more 
gas to be taken into lungs, as if patient had increased his minute 
volume. when you add N2O to other inhalant anesthetics, it will add some 
anesthesia - reduces amount of other drug required to produce anesthesia 
- reduces MAC. two advantages - if primary agent is really expensive, and 
N2O is cheap, can be cost effective, decreasing cost of anesthesia. if 
primary agent has a lot of dose dependent cardiovasc. depressant effects, 
adding N2O, decreasing primary agent, will decrease those effects. how 
clinically important is this? in humans, MAC for N2O is aobut 100%. so if 
a person inhales 50% N2O, and MAC is 100%, that's 1/2 mac, so you can 
decrease primary agent by about 50%. in animals, mac is closer to 200%, 
so 50% N2O is only 1/4 MAC, so you can't reduce the other agent as much. 
so sometimes it could be useful, but usually this isn't useful. other 
methods are used to get cardiovascular stability. but N2O is commonly 
used in people, and was once used a lot in vet med.

some undesirable 
effects of N2O and times to avoid it:
gases including inhaled anesthetics 
move down concentration gradient from machine into patient. if there are 
pockets of gas in the patient, inhaled gas will enter those pockets and 
equilibrate. when agent is given in low concentration as halothan and iso 
are, increase in gas volumes in pockets isn't important. but N2O is given 
in high concentrations, so increases in volume are significant. if 
patient inhales 50% N2O, volume of gas pocket would double at 
equilibration. at 80% N2O, gas volume will increase 5 times! could get a 
really distended gut! it takes time for gas to equilibrate in GI tract 
but it starts with the first breath. equilibration in dogs in GI tract 
takes about 200 minutes. most people think of gastric torsion - gas is 
trapped in stomach, compression of mucosa, impairment of blood flow =- if 
you give N2O to that patient volume in stomach will increase, pressure 
will increase - rupture? even in normal dogs, this is awkward to 
dangerous. if you give N2O over time to a spay dog, gas in gut will 
increase during surgery, bowel will distend, start coming out of 
incision. by the time you're done, guts will all be distended andout of 
the abdomen. this is painful and increases potential for infection. also 
causes water loss due to large surface area exposed to air. then you have 
to stuf guts back in and sew up the animal and it wakes up uncomfortable.


where else is gas in the animal to cause problems? chest. animals with 
pneumothorax - equilibration in IP space takes only 20 minutes. a small 
pneumothorax not interfering with ventilation can result in life 
threatening situation due to increase in gas volume if given N2O. 

when 
might you consider using N2O?
some smaller animals are induced in a 
chamber - cat in fishtank idea. during induction there may be excitement. 
if you add N2O, it will speed induction and may decrease excitement. but 
you have to consider what happens next - you take animal out of box and 
it starts breathing air. N2O will come out of blood rapidly since not 
that soluble. it mixes with air in alveoli, reducing available oxygen. 
this is diffusion hypoxia. this could also happen at the end of the 
procedure, if you used N2O and you disconnect the animal from the 
machine, the same thing happens as animal begins to breathe room air. so 
you have to leave the animal on 100% O2 for a few minutes so it breathes 
out the N2O. also with C-sections, if you anesthetize a mother w/N2O or a 
mix including it, the neonate starts breathing room air, and the N2O will 
do the same thing in his alveoli. 

N2O interferes with B12 and causes 
signs of deficiency - see handout.

it's abused. it comes in blue tanks. 
we don't use it in VHUP anymore but there are a few tanks around. theft 
of N2O occured here. practicioners who use N2O often keep buying tanks 
and when they go to use it, tank is empty - because someone working there 
has been stealing it. 

whipped cream - the stuff in cans you buy is 
whipped with N2O - people try to get it out of the can - if you don't 
shake the can, and don't turn it upside down, and push the button, the 
gas comes out. so sometimes you get a can and you cant get the whipped 
cream out because someone sucked out the gas.

drug used to treat 
malignant hyperthermia - dantrolene. this dz occurs commonly in pigs and 
people, more common in some breeds of pigs than others. also seen in 
other spp with reduced frequency. this is due to excessive Ca++ release 
from SR. this causes skeletal muscle hyperactivity, increased 
temperature, increased production of CO2, increased O2 consumption. temps 
go up to 108, 110, and death is the common outcome. symptomatic tx - 
helps occasionally but rarely. usually affected animals die. it was found 
that dantrolene could be used to tx this condition. it decreases release 
of Ca++ from SR. so it, by an intracellular mechanism, impedes the 
mechanism of the dysfunction. other tx - NM blockers, etc, have no 
effect, since problem is intracellular.

dantrolene sodium aka Dantrium 
IV - this drug can save these patients. the anesthetic triggers for this 
problem are succinylcholine (depolarizing NM blocker) and all the potent 
inhaled anesthetics except N2O.

substance abuse: the drugs we use in 
animals are abused by people. substance abuse is a big problem. medical 
community is liable due to stress and availability. covering up for or 
ignoring the problem in a friend or relative won't help anyone, delays 
treatment, and may end up killing someone.

we've gone over a lot of 
drugs. we may feel stressed. but as you start working with and thinkin 
about drugs, fog should lift. 
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