Notebook: Anesthesia

Injectable anesthetics: rapidly acting anesthetics (examples: thiopental, propofol, etomidate, ketamine); slow acting (examples: potent opioids, neuroleptanalgesics)

BARBITUATES
- mechanism of action: allosteric modulation of the GABA A receptor
- increase in average duration of GABA-activated Cl- ion channel openings

Other mechanisms of action -- keywords for CNS: interaction w/ central Ca2+ and Na+ channels, glutamate and nicotinic ACh receptors. Depression of autonomic ganglia. keywords for PNS: block ACh effects at nicotinic synapses, inhibition of transmembrane Ca2+ fluxes

What do barbituates do?
- gradually depress the CNS (anesthesia)
- (don't provide analgesia)
- decrease EEG activity
- decrease cerebral blood flow
- decrease intracranial pressure
- provide anticonvulsive activity

Undesired effects of barbituates?
- central respiratory depression (i.e. hypoventilation)
- cardiovascular depression
- decrease in cardiac output
- decrease in arterial blood pressure
- may cause tachyarrhythmias
- decrease in renal blood flow
- decrease in hematocrit
- decrease in white blood cells
- perivascular injection may cause thrombophlebitis

Pharmacokinetics: How are barbituates eliminated?
- metabolized in the liver; conjugated with glucuronic acid
- renal excretion

Case in point: thiopental (pentothal)
- indicated for brief surgeries/ exams, neurosurgical patients with increased intracranial pressure, induction of general anesthesia, immediate control of convulsions

PHENOLS
- unrelated to barbituates
- main mechanism of action:
- allosteric modulation of GABA A receptor

What do phenols do?
- gradually depress CNS
- intravenous deep sedation
- non-hypnotic CNS effects:
- decrease cerebral blood flow
- decrease intracranial pressure
- antiemetic effects
- can be used for general anesthesia
- decrease EEG activity
- no analgesia

Undesired effects of phenols?
- respiratory system
- central respiratory system depression
- bronchodilation
- inhibition of laryngeal reflexes
- cardiovascular system
- hypotension
- transient excitatory effects

IMIDAZOLE (ETOMIDATE)
- good for inducing anesthesia in high-risk patients
- mechanism of action: allosteric modulation of GABA A receptor
- no analgesic effects
- decrease in EEG activity
- decrease in cerebral blood flow
- decrease in intracranial pressure
- cons: occasional CNS excitatory effects, hemolysis, pain, inhibition of adrenal steroid genesis

CYCLOHEXANONES
- ketamine, tiletamine. "dissociative anesthesia"
- loss of consciousness
- catalepsy
- maintenance of protective reflexes
- skeletal muscle movements
- mechanism of action: blocks NMDA receptor
- decrease in central glutamatergic activity
- provides analgesia and anesthesia

INHALANT ANESTHETICS
- inhalant anesthetic dose required to maintain an appropriate surgical plane of anesthesia is lower in older animals than in younger animals
- the speed of upake of inhalant anesthetics into the blood is inversely related to blood solubility and cardiac output
- inhalant anesthetics commonly cause vasodilation and negative inotropic effects
- they suppress the effects of excitatory neurotransmitters such as glutamate and ACh within the CNS
- inhalant anesthetics: degree of hepatic metabolism (ranked highest to lowest) is sevoflurane > isoflurane > desflurane > nitrous oxide
- the minimal alveolar concentration (MAC) of an anesthetic agent prevents gross purposeful movement in 50% of subjects exposed to a supramaximal noxious stimulus.

Isoflurane
- causes more significant cardiovascular depression than sevoflurane.

Sevoflurane
- sevoflurane is less potent than isoflurane
- sevoflurane allows for more rapid adjustment of anesthetic depth during anesthesia than does isoflurane
- In general, renal toxicity is not a common problem with sevoflurane.
- sevoflurane is more lipid soluble than desflurane

Desflurane
- desflurane is a halogenated ether
- desflurane has a more pungent odor and irritates airways more than sevoflurane does
- recovery of anesthesia from desflurane is faster than from isoflurane
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Updates: Marine Symposium 2-18-2009

Next Wednesday, February 18, please join us at the University of Pennsylvania School of Veterinary Medicine Hill Pavilion Auditorium for an experience in marine conservation education.

Dr. Enric Sala, PhD -- a National Geographic Explorer -- along with Dr. Alonso Aguirre, DVM, PhD -- co-founder of the Consortium for Conservation Medicine -- will be dazzling us with their speaking abilities. Check out the flyer at left (designed by yours truly)! And check out our facebook group as well.

Details below:

Join us for a UPenn “Year of Evolution” event focused on the critical issue of marine species conservation – recent groundbreaking discoveries and innovative solutions to save our oceans. Famed marine researchers and explorers will share their findings and recount their global adventures, tracking and protecting endangered marine species.

Featured speakers:

ENRIC SALA, PhD, National Geographic Explorer, Pew Marine Conservation Fellow, and key player in the recent establishment of the largest marine reserve in the world.

ALONSO AGUIRRE, DVM, PhD, co-founder of the Consortium for Conservation Medicine, leading expert in marine mammal and sea turtle conservation.

Presented by Special Species Club, EcoVet, and IVSA, with generous sponsorship from Merial, the Office of the Provost, and Public Health Club.

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Updates: Blogging about a Blog

Sapna Magazine has a blazing blog going lately! Vaishali Rao, our director of communications, is currently our resident blogger -- and she's been posting on a diverse array of interesting topics.

Recent topics have explored fashion, politics, consumerism and the arts. For example, who knew that Britney Spears hired a Bollywood-inspired choreographer for her Circus world tour? The blog also put a spotlight on the success of South Asian American supermodel Lakshmi Menon. (Check out Menon's model bio on New York Magazine's website.)

The following is an excerpt from the Sapna blog:

Britney chose Indian choreographer, Rujuta Vaidya, trained by famous Bollywood choreographer Saroj Khan, to help her hit her moves.

“Britney was not used to the Bollywood style of dance but she is a fast learner and she picked it up well. I know she was excited about doing it because she is the one who selected us,” Rujuta told a New York-based website.

Can she pull it off? Or will it look like more of a Circus than it's supposed to?

Visit www.sapnamagazine.com and scroll down to "the Sapna blog" to read more!
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Notebook: Hemostasis -- Coagulation

The following notes were taken during a 2-hour lecture by Dr. Urs Giger, DipACVIM.

Brief introductory discussion on the molecular level:
- activation of protein C.
- in order to be functional, protein C has a cofactor (protein S)
- both protein C and protein S are vitamin-K-dependent factors.
- complex of protein C and S will inhibit factors 5 and 7
- complex will also activate the inhibitor of plasminogen activator.
- this is a very regulated system that has to be balanced.
- Imbalances will lead to either a tendency to bleed or a tendency to thombose.

When an animal has a clotting problem, we need to know if the problem is primary or secondary. Problems may be acquired (any time, any age) or hereditary (for example, von Willebrand disease and hemophilia).

When an animal presents, ask the owner if there is a possibility of rodenticide problem.

During the physical exam, characterize bleeding.

COAGULOPATHIES: Problems with Secondary Hemostasis
- use a diagnostic test to assess hemostasis
- cuticle bleeding time: assesses overall hemostasis. Not standardized, painful.
- this method doesn't differentiate between problems with primary and secondary.
- "an absolute must" for every patient: blood smear evaluation
- look for platelets; if absent, ask yourself: is this a true thrombocytopenia?

Additional diagnostic testing
- do this prior to treatment (most situations -- unless patient is critically ill)
- why? b/c any treatment you do may change these results.
- Citrate tube: Tube contains 3.2% citrate solution that is added to the blood.
- Remember, without calcium, there is no coagulation
- The citrate is in a molar form, so calcium binding is a reversible process.
- (An EDTA sample chelates calcium and therefore is irreversible.)
- To perform the test, the tube must contain 9 parts blood and 1 part citrate.

- Collection technique is very important:
- if technique is incorrect, you may activate the coagulation pathway
- this may leave to shortened coagulation time.

- Activated Coagulation Time
- uses surface activation
- does not involve extrinsic clotting pathway
- does not require instrumentation
- does not require anything but the tube containing diatomaceous earth
- use vacuutainer; once first drops of blood are in the tube, start the timer
- when it is filled, pull it off; make sure there is good hemostasis
- mix by gently rotating the tube in your hands
- results: if there are no platelets, the actual clotting time will be prolonged.

[2nd HOUR OF LECTURE]

Partial Thromboplastin Time (laboratory PTT/aPTT)
- reactants: calcium, PTT activator (phospholipid), plasma
- phospholipids need to be added b/c plasma lacks platelets
- results are given in unit time, not in percent or in amount of protein
- in a way, it's assessing the same systems as ACT (intrinsic & common pathways)

Prothrombin Time (laboratory PT)
- assesses the extrinsic and common pathways
- reactants: calcium, tissue factor, plasma
- assay can be done within an hour; results are very reliable.

Protein Induced by Vitamin K Antagonism or Absence (PIVKA test)
- important for the main reason of anticoagulative rodenticides
- similar or identical to PT
- it is NOT specific for rodenticide poisoning.
- no reason to do this anymore. (PT test gives the same information)
- note: PTT test is most useful.

Fibrin degradation
- two ways to estimate fibrinogen:
- Thrombin Time (TT)
- not affected by rodenticides
- Plasma Fibrinogen Quantity

Thromboelastography
- overall hemostatic evaluation
- can predict thrombotic tendency
- can suggest fibrinolytic activity

Extra notes on hemostasis:
- Heparin is a very good coagulation inhibitor.
- Remember, you CANNOT DO coagulation tests with serum.
- The difference between serum and plasma: COAGULATION FACTORS -- mainly FIBRINOGEN.
- Schistocytes (spelling?) are seen when there are fibrin strands in a blood vessel.

Note to self: See Dr. Giger's lecture handout and complete the table on the second to last page.

TRANSFUSION MEDICINE
- indication for transfusion: anemia
- plasma may need to be given, or a combination of plasma and RBCs

Blood types are genetic markers on RBC surfaces; these are species specific and may differ between individuals.

Note to self: See more info on transfusion medicine in Dr. Giger's lecture handout.
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Opinions: the Aerial Gunning of Wolves

For years now, the Defenders of Wildlife has been sending me alerts on the brutal killing of wolves in Alaska. I've always opposed the savagery that's been documented in bloody photos and videos, but not until today did a classmate make me think: Why is Alaska doing this? What is the motivation? Does the wolf population need to be managed, and if so, why?

Even if the wolf populations are in need of management, there needs to be a humane way to control their populations. However, she inspired me to do some digging.

My research yielded the following: Wolves are being targeted because they are killing their natural prey, caribou and moose, in their Alaskan homeland. A natural prey-predator relationship that the governor wants to stop? Why? There's got to be a motive... And here it is.

Here's an old clip from the Seattle Times (December 8, 1992):

We Should Learn From Alaska's Big, Bad Wolf Mistake
by John A. Baden, Ph.D. and Robert Ethier

KILLING WOLVES is a dramatic and highly controversial wildlife management practice. Alaska has recently proposed this as a way to boost caribou, moose, and deer populations for tourists and hunters.

But many people find gunning wolves from airplanes offensive and are outraged.

The logic underlying the killing seems clear, but the issues are complex. Wolves do kill caribou, elk and moose - especially their young. Reducing wolf populations should increase the numbers of these ungulates, but by how much? There are bitter disputes among scientists over the size of predator impact upon prey populations. Read full article

In a nutshell, it seems that these wolves are being killed so that hunters can come in and have lots of caribou and moose to kill? So... The wolves are being killed because they're doing as nature intended... So that hunters can come in and fulfill a disgusting blood lust for the thrill of the chase?

My research is far from over on this issue, so there will be more updates to come. But I maintain: Even if population management is warranted, there are more humane methods that can be used. After all, hunting by aerial gunning has been illegal in the United States since 1972, and with good reason.

Humane methods of population control will be detailed in a future post.
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Notebook: Electrocardiography 3

These notes were taken during a lecture by Dr. Meg Sleeper, veterinary cardiologist.

- Ectopic beats come from outside the sinus node; they can be either early or late.
- Junctional beat is the same as an AV nodal beat
- Junctional escape vs. ventricular escape

BASIC ECG CLASSIFICATION
- aberrant conduction (the conduction path is abnormal)
- bundle branch block (RBBB) occurs commonly.
- right bundle branch block occurs most commonly.
- left bundle branch block is more often associated with structural heart dz.
- arrythmia (either of supraventricular or ventricular origin)

2 differentials for a wide QRS complex:
- ventricular aberrant beat (a ventricular complex)
- block in conduction (blockade through conduction through the ventricles)
- with a RBBB, you see negative deflection

SUPRAVENTRICULAR CARDIAC RHYTHMS

Classification of conduction defects
1st degree: prolonged PR interval (slower than normal conduction through the AV node
- can be caused by fibrosis of the AV node, or certain drugs (i.e. digoxin)

2nd degree type 1 or Wenchebach: some of the P waves don't get through. Unconducted p waves typically occur as the R to R interval is lenghtening. May see subtle lengthening of the PR interval.
- in a dog where this is physiologic, increasing sympathetic tone will cause this to go away (i.e., running the dog in the hallway for a bit)

2nd degree type 2: P wave that is not followed by a QRS complex. Most typically it is progression of AV disease or fibrosis. (If this animal is exercised, the rhythm won't go away.)

3rd degree: complete AV block. Nothing is conducting down. It may seem that the P waves are very regular on their own and the QRS complexes are very regular on their own; however, the regularity of the two may not seem to be related. T waves are wider than normal with discordant QRS complexes.

Asides:
Remember, the first heart sound is caused by closure of the mitral valve. Premature beats are usually very loud b/c they occur when the valve is wide open.

Summation occurs when two cardiac events appear on the ECG paper at the same time.

If a QRS is not very wide, it may be coming from the AV node.

Case example: Dog has been fainting; ECG shows a sinus bradycardia with a ventricular escape beat. Atropine an be given as a diagnostic test (Atropine Response Test).

If the pattern goes away in response to atropine, the pattern is a sinus tachycardia. (A normal dog would also respond this way.) This means that the heart can respond normally when vagal tone goes away. For some reason this dog has abnormally high vagal tone. Note: If the dog had not presented for fainting, and the atropine response test caused the pattern to go away, this dog probably would not need to be treated.

Sinus rhythm is common in cats but pretty rare in dogs. Sinus arrhythmia is common in dogs. Remember, an arrhythmia is not necessarily abnormal. Sinus tachycardia is a normal response to pain, fever, stress, fear, etc.; this is a way the sinus node responds to elevated sympathetic tone.

Supraventricular tachycardia is also known as paroxysmal atrial tachycardia. If vagal tone is increased, does this slow down gradually or abruptly? -- To answer this question, the carotid sinuses or eyeballs are pressed as a (tentative) diagnostic test (this doesn't always work). If the pressure is released and the pattern resumes abruptly, the pattern is a supraventricular tachycardia. If the pattern resumes gradually, it is a sinus tachycardia.

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Notebook: The Dairy Industry

These are notes taken while in lecture (2nd hour) on February 5th, 2009.

- The export market is very important to the industry.
- Prices are determined by supply and demand for dairy products worldwide.
- Regarding current milk price, the Feb. Class I cost suffered a ~$5 loss since last year.

Lately, the dairy industry has had to put a lot more of its product in storage. The melamine scare has caused harm to the dairy industry.

Today there are about 200,000 too many cows in the dairy industry (too much milk is being produced).

In the U.S., demands are expected to continue to grow. Regional shifts are occurring in the U.S.; larger herds will influence the market. In PA, agriculture is the number 1 industry (~1 of each 6 people is employed in agriculture). The top 6 commodities in PA: dairy products, cattle and calves, mushrooms/ agaricus, corn, greenhouse/ nursery, chicken/ eggs. The average number of PA milk cows (annually) is about 550,000.

Milk in PA is produced primarily in the southeastern part of the state. PA ranks number 5 in the U.S. in total milk production. PA also ranks 4th in cow numbers and 15th in milk production per cow.

MILK SAFETY
- milk is one of the most monitored foods!
- the primary control of milk/ milk products is carried out by State officials.
- the FDA regulates the use of animal drugs and feed additives
- FDA also establishes regulations for safe residues in milk.

Control of milk safety:
- Somatic Cell Counts are done to measure mammary gland inflammation
- Legally, there should be a max of 750,000 cells per mL.
- Bacteria counts are also done and the limit is 100,000 per mL.

ORGANIC MILK PRODUCTION
- ruminants must be let to pasture for a certain percentage of the day

Note to self: see slides for more info.

LACTATIONAL PHYSIOLOGY
- cows with BST in their milk have higher milk production
- BST is bovine somatotropin (growth hormone)
- BST is naturally occurring
-- recombinant BST is a genetically engineered duplicate.
-- this recombinant is made using the same technology that is used to make insulin.
-- it enhances a cow's natural BST.
-- concerns about the safety of rBST are not scientifically supported.
-- studies have shown that BST is inactive in humans.
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Notebook: Equine Respiratory System 3

These are notes taken on cases presented by Dr. Rose Nolen-Walston.

Diagnostic plan fever and abnormal lung sounds: rads, ultrasound, sample.
Rads: miliary pattern. Only a few causes: cancer (metastases), sepsis, fungal dz, silicosis. Nothing good that looks like this on rads! Probably not viral or bacteria.

Plan at this point: How to sample? Use BAL (not trans trach) because it's diffuse. Get fungal hyphae, indicates fungal pneumonia, which is rare. Can be primary or secondary (usually secondary doesn't cause a problem). If suspect primary, get a travel history. Treat with systemic anti-fungals. Tends to be $, and prognosis is poor. Best treatment: Itraconazole. (Case study presented in class resulted in full recovery).

Up to 70% of trach washes have fungal hyphae; THIS IS NORMAL! Do not treat with anti-fungals unless you see evidence of fungal pneumonia: i.e., large numbers of intra and extracellular fungal elements, consistent rad changes, or history.

Pneumocystis (and others) is an opportunistic bug (i.e., SKID foals, recent GI dz, other reasons for immuosuppression). Exactly the same diagnostics, but also test for immune function. Prognosis is poor.

Other possibility for miliary pattern: Interstitial pneumonia (pretty rare)
- present with severe clinical signs, i.e. cyanosis, profound respiratory distress, wasting away, cough, fever, pretty hypoxemic
- diagnose with rads (parenchymal disease)
-- pattern must be diffuse. Do BAL.
- Interstitial pnuemonia may be associated w/ viral dz (like flu), systemic inflammation (ARDS), equine nodular pulmonary fibrosis (may be associated w/ EHV5, pattern looks more nodular than miliary), silicosis: granulomas form around silicon, or ideopathic
- treatment is often futile. Euthanasia often elected if owner decides not to treat. (If you sit and wait, the horse may be fine!)
- prognosis is guarded to poor.

Case presented: foals with puffy joints, no lameness
- if foal w/ puffy joints is lame: septic arthritis (EMERGENCY)
- on ultrasound, see what may be neoplasia/ abscess/ granuloma
- rads pathognomonic Rhodococcus equi.
- Rhodococcus equi causes abscess-forming pneumonia.
- puffy joints but not lame: don't tap
- diagnosis: use cytology (pleomorphic cocci), culture, PCR
- on PCR, only VapA is really bad
- transmission: shed in feces
- use macrolides to treat b/c they go into the cell. Azithromycin stays at effective levels in pulmonary macrophages for 30 days! Treat with macrolides + rifampin.

- Rhodococcus is not the only thing that causes pneumonia in foals: top cause is Strep. zooepidemicus. Diagnose with imaging (rads/ US), sampling (trach wash). Put on broad spectrum (but not penicillin).
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Notebook: Equine Respiratory System 2

Treating pleural pneumonia Start with broad spectrum antibiotics (4 quadrant coverage): penicillin, gentomycin, metronidazole. Gas specks in lungs (on ultrasound) probably indicate anaerobic infections; also brown or red nasal discharge and stinky breath. These horses need to be put on metronidazole. Strep. zooepidemicus is the number one isolate; enrofloxacin doesn't get it! Oral drugs: TMS (nice but a lot of resistance), doxycycline, rifampin (not rifampin by itself!).

Will often put on anti-inflammatories (NSAIDs) to increase patient's comfort level. Remember to consider effects on kidneys and stomach. Use thoracic drains if necessary (if there's a lot of fluid). Support with calories very very early.

Increased pleural effusion decreases lymphatic drainage, leading to edema.

When do you stop the antibiotics? Recheck frequently with US (consolidation and abscesses), check fibrinogen and WBC counts, make sure afebrile for 4-5 days afterwards. May also re-check the tracheal wash (though a bit invasive).

Can do rib resection if you encounter "pizza pleura."

Epidemiology: Young racehorses being shipped are at top risk. Next is esophogeal obstruction in older horses, then post-anesthesia and recent viral infection.

Aspiration: When horses aspirate, it goes to the "triangle of death."

Prognosis is good for pleural abscess; horses with pleuritis -- prognosis is a lot worse.

Lympadenopathy, fever and nasal discharge is strangles (Strep. equi equi) until proven otherwise! Gets submandibular and retropharyngeal lymph nodes. Let the dz run its course; treat symptomatically; may want to use NSAIDs; drain abscesses when they're "ripe"; more severe cases will need tracheostomy; put complicated cases on penicillin. Prevention: isolate effected horses until they have a negative culture. May need to identify carriers if barn problems persist. Rare to get strangles twice. 2 vaccines available: new intranasal modified live vaccine is much more effective than the other vaccine. Always give it as the last vaccine because it is a modified live vaccine!

Bastard strangles: metastatic strangles. Lymph nodes in any part of the body are affected; can end up with problems in brain, liver, kidney etc. Diagnose with a titer for Strep. M protein. Treatment: long-term antibiotics. Penicillin works well.

Immune-mediated problems associated with Strep:
Purpura hemorrhagica is a vasculitis associated with the body getting confused by the Strep. Results in severe edema. Penicillin and corticosteroids; good prognosis. If outbreak, don't vaccinate horses that have possibly been exposed! Greater chance that they will develop purpura. Only vaccinate horses that you are really sure have not been exposed.
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