Sunday, July 24, 2011

Notes from July 2011 St. Louis AVMA Conference-Anesthesia and Analgesia

These are papers from the July 2011 St. Louis AVMA conference.  I’ve edited them to delete some of the vet only jargon and for space considerations.  If you see (…) that means that information has been deleted due to these considerations.  The ones listed here include HCM, and other heart related papers, treatments, papers on x-rays and echos, thrombosis, kidney disease, idiopathic cystitis, pain management, anesthesia and cardiac disease, supplements and other hazards for pets, and some other basic information I hope is helpful.


Gwendolyn L. Carroll, DVM, MS, AB, Diplomate ACVA, Diplomate ACAW

Texas A&M University, College of Veterinary Medicine and Biomedical Science

Analgesia and anesthesia protocols in cats may be particularly complex due to their

physiologic, anatomic, and behavioral differences from dogs.  Cats lack the metabolic pathway

that allows them  to conjugate drugs or their metabolites with glucuronide.

Perioperative pain in cats has been closely examined over the last few years, but what about

chronic pain from cancer, arthritis, and other debilitating medical diseases?  There is now a

great deal of evidence that degenerative joint disease (eg, osteoarthritis, perhaps

spondyloarthropathy) is more prevalent in cats than we believed. A study at North Carolina

examined the prevalence of radiographic changes in 100 geriatric cats (>12 years) that were

presented for something other than musculoskeletal disease. Radiographic evidence of

degenerative joint disease was found in 90% of cats. Neurologic disease was associated with

lumbosacral lesion in the vertebral column. Seventeen of the elbow joints had severe lesions.

There is no question in my mind  that cats that become cranky as they age have chronic  pain.

Until recently we have had nutraceuticals and aspirin to treat those cats.  Now, we have more

options.  Alternative methods of drug delivery are being  investigated, such as  transdermal gels,

transnasal, time-release encapsulations, and transmucosal patches.  There are also several

techniques for post-operative analgesia, such as, regional techniques.  Unfortunately, for

systemic  administration, most analgesics are given  PRN rather than on a schedule based on

their pharmacokinetics (eg, every 4 hours).  For unremitting pain, constant rate infusions (CRI)

are administered (eg, fentanyl, morphine, ketamine). If patients are eating and  the

bioavailability of an analgesic is suitable, oral administration may be used (eg butorphanol,

fentanyl  lollipops).  Topical administration (eg, transnasal butorphanol, transdermal fentanyl,

topical morphine, topical lidocaine) may be used if the agent lends itself  to topical application.

A cautionary note about transdermal gel preparations: confirm that the pharmacokinetics have

been determined by that route in the target species and that the patient is not  licking  them off

(then it is oral and susceptible to first pass metabolism).

The administration of opiates to cats may result in some excitement…There is speculation that excitement occurs as a result of a different opiate receptor population in cats…

The potential for excitement has altered my treatment regimens in cats. I may avoid  pure μ-agonists in non-painful cats or administer them with a tranquilizer, such as acepromazine (0.05 mg/kg, SQ, IM) if there are no

contraindications.  Mu-agonists include morphine, oxymorphone, hydromorphone, and fentanyl (all Schedule II).

Mu-agonists provide excellent analgesia (good  for moderate to severe pain), although duration

of action is agent specific. Administration of μ-agonists is associated with respiratory

depression and vagally-induced bradycardia.  As mentioned earlier, sedation is species

dependent; dogs have CNS depression and  cats have CNS excitation.  In cats, μ-agonists may

result in hyperthermia (hypothermia in dogs) and mydriasis (miosis in dogs).

Morphine is the gold standard to which all opiates are compared.  Historically, morphine was

believed to result in hyperexcitability in cats, but the hyperexcitability is

now believed  to result from very large doses administered to non-painful cats.  The advantages

of morphine are: systemic (IM) and regional (epidural, intraarticular) administration and,

morphine is cheap. The disadvantages include histamine release when administered  IV,

respiratory  depression. vomiting, pruritis, urinary retention... Side effects may be purring, loss or

increase in appetite, agitation, dementia, heightened responsiveness, and dilated pupils.  There

is a potential for respiratory depression, urinary retention, constipation, and bradycardia.

Opiate agonist-antagonists are appropriate for mild to moderate pain. There is a ceiling effect

for analgesia and  respiratory depression; mixed agonist-antagonists are less likely to cause

dysphoria. The agonist-antagonist approved as an analgesic in cats is butorphanol

(Torbugesic-SAR 2 mg/ml); other available forms are TorbugesicR 10 mg/ml, TorbutrolR 0.5

mg/ml, and oral antitussive tablets.  Butorphanol may be administered SQ, IM, IV, or orally and

may be used as a μ-antagonist.The dose in cats is 0.2-0.4 mg/kg, IV, SQ, IM. For oral dosing,

1 mg/kg every 4 to 8 hours may be used. In a pilot study looking at PO, transdermal (TD), and

transmucosal (TM) butorphanol, bioavailability of TM butorphanol (38%) was greater than PO

(30%); TD butorphanol did not result in measurable plasma concentrations.

Nalbuphine (NubainR, not scheduled) is not as efficacious an analgesic as butorphanol.

Nalbuphine provides visceral analgesia for about 2 hours at 0.75, 1.5, and 3.0 mg/kg, IV. But it

is generally used  to antagonize μ-agonists, while maintaining analgesia at κ receptors (also

some effect at sigma receptors). I generally mix 1 ml nalbuphine (20 mg/ml) with 9 ml saline

and titrate to effect.

Buprenorphine (Schedule III) is a partial μ-agonist. Partial μ-agonists behave similarly to

agonist-antagonists. Buprenorphine has a high affinity for μ-receptors (even μ-antagonists may

have difficulty removing partial μ-agonists from the μ-receptor), but not much activity once

occupying the receptor. Buprenorphine is appropriate for mild to moderate pain.

Buprenorphine is relatively inexpensive. If respiratory depression occurs, it is very difficult to

antagonize. The dose is 5-10 μg/kg, IM, IV, +SC and the duration is 6 to 8 hours.

Buprenorphine may be administered epidurally in cats; 5 to 10 μg/kg is the reported dose, but I

would use 3 to 5 μg/kg. The duration of epidural buprenorphine is about 12 to 18 hours.

Presentation of a recent abstract indicated that TM buprenorphine is 100% bioavailable in cats

and provides good analgesia in a thermal model…The cats accepted  the TM

buprenorphine without frothing, foaming, biting, or scratching. The implications for cat owners

are huge.

There are rarely indications for antagonizing μ-agonists in painful patients. Naloxone (NarcanR;

0.02 mg/kg, IV, IM, SQ or 0.5 ml [0.2 mg] diluted to 5 ml with saline and administered IV to

effect) is a μ-antagonist. Antagonists are not analgesics, and actually antagonize analgesia in

addition to antagonizing the cardiorespiratory depression of opioid agonists.  In human

medicine and anecdotally in veterinary medicine, acute antagonism of opioids in painful

patients may precipitate arrhythmias and death.

Alpha2-agonists have previously been implicated  in anesthetic misadventures involving cats.  It

is difficult to separate the drug effect  from  other effects that may have co-existed.  Many studies

have been conducted  on xylazine and medetomidine in cats. Caution is always indicated when

using potent cardiovascular depressants (decrease in cardiac output, stroke volume, and heart

rate with either no effect or a decrease in oxygen, and  no effect in arterial blood pressure, pH,

or carbon dioxide tensions). Dexmedetomidine has a relatively short analgesic duration and

prolonged sedation and may precipitate vomiting.  Dexmedetomidine, the most recently

released α2-agonist for small animals in this country is specifically approved for use in cats.

Dexmedetomidine works well for sedation in cats (particularly with butorphanol) for restraint,

Dexmedetomidine (0.005 mg/kg IV, SC, IM) has been used as a premedicant in cats for

inhalant anesthesia and postoperatively for analgesia and sedation (0.001 mg/kg IV, SC, IM).

The effects of α2-agonists are synergistic with those of opioids, but the perioperative dose to

be used in combination with opiates has not been reliably determined.  When used in

combination with opioids the cats should be closely monitored and oxygen should be available.

The effects of α2-agonists may be antagonized  with α-antagonists such as atipamezole,

yohimbine, or tolazoline. Similarly to opioids, the antagonism of α2-agonists in painful patients

is not without risk.

Ketamine at low dosages (0.5-1.0 mg/kg, IM) may be used to provide somatic analgesia

without cataleptoid effects; 2-4 mg/kg, IM, IV may provide 30 minutes of somatic analgesia.

Ketamine boluses or CRI are particularly helpful in patients with burns or skin wounds and in

patients with chronic pain due to the effect of N-methyl-D-aspartic acid (NMDA) antagonists on

wind-up. I would not hesitate to administer a priming dose of ketamine (0.2-0.5 mg/kg IV)

followed by a ketamine infusion (2-10 μg/kg/min IV) in cats with good kidneys and no cardiac

disease.  Ketamine (2 to 10 mg/kg TM) is well absorbed through the buccal mucosa and may

be administered by this route in traumatized patients where administration of other agents or

restraint is not realistic.

NSAIDs have not been extensively used in cats due to toxicity…(reactions to drug)  included apparent depression,

weakness, cyanosis, facial edema, methemaglobinemia, lethargy, and somnolence…Newer NSAID’s with fewer GI and renal side-effects are being  used.  It is important to understand that  NSAIDs should only be used in healthy young normotensive normovolemic cats with no evidence of gastric ulceration, bleeding diathesis, or compromised renal function...If NSAIDs are administered preoperatively, intraoperative IV fluids

should be given, acepromazine should be avoided, and  blood pressure should be monitored.

Do not use NSAIDs in conjunction with corticosteroids or in patients on other NSAIDs without

an appropriate withdrawal period. Potent prostaglandin inhibitors should  not be used preemptively

due to the potential for hemorrhage and the potential for renal damage if hypotensive during anesthesia.

Meloxicam and robenacoxib are approved  for use in cats. There is no reason to use an off

label NSAID in this country.

What does that mean?  It is complicated.  Meloxicam was the first NSAID approved  for use in

cats. Meloxicam was the first veterinary product to get a black box for a use for which it was

not labeled.  There are approved doses for extended oral dosing in Europe1 (Initial treatment is

a single oral dose of 0.1 mg meloxicam/kg body weight on the first day.  Treatment is to be

continued once daily by oral administration (at 24-hour intervals) at a maintenance dose of

0.05 mg meloxicam/kg  body weight.  To be administered orally either mixed with food or

directly into the mouth); this is consistent with the dose range finding study conducted here.

there is a dose range finding study for osteoarthritis. Often the drug  is administered  every  other

day, twice a week, or at a dose of 0.1 mg/CAT. These are off  label and against the black box

label-see above…

There are several drugs that are being investigated as analgesic adjuncts, particularly for pain

that is refractory to opioids and NSAIDs.  Gabepentin is useful for neuropathic pain (eg neuritis,

nerve entrapment, disc disease, post-laminectomy). The suggested range for cats is 2.5 to 5

mg/kg q 12 hour.  Wean off slowly and reduce the dose in renal  insufficiency.  Pain from

inflammatory  bowel disease and interstitial cystitis may be treated with amitriptyline (2.5-12.5

mg/cat q 24 hour PO) or imipramine (2.5-5 mg/cat q 12 hour PO). Remember that tricyclic

antidepressants may interfere with your drug choices for anesthesia (eg, meperidine is

contraindicated, anticholinergics should only be used as necessary).

Benzodiazepines (Schedule IV) are not very good  tranquilizers in cats. Their effects are

unreliable when used alone in adult healthy animals. Benzodiazepines are more reliable when

combined with a sedative or used in really young, really old, or very sick cats.  Midazolam (0.2

mg/kg, IV, IM, SC) is a short acting water soluble benzodiazepine that may be used in place of

diazepam (0.2 mg/kg, IM, IV) as part of induction with a hypnotic or dissociative (eg. etomidate

or ketamine), in combination with an opiate (eg. butorphanol or fentanyl) as a premedicant, or

as part of an infusion (eg. fentanyl) to decrease the minimum alveolar concentration (MAC) of

an inhalant. Flumazenil may be used to reverse the effects of benzodiazepines; titrate it to

effect.  Propofol (2,6-diisoproylphenol) (4-8 mg/kg, IV) is a non-barbiturate hypnotic that is noncumulative.

Since recovery is very fast, it has gained some popularity.  It is important to

remember that the adverse cardiovascular effects from propofol are very similar to those of

barbiturates, the effects are just short-lived.  Slightly higher doses are required for cats than

dogs and recoveries are longer in cats than dogs when the infusion lasts more than 30 minutes

(probably due to decrease glucuronide conjugation). Beware of phenol conjugation.  There are

new formulations of propofol (longer shelf life) which have been approved and not yet

released….Etomidate (0.5 - 1.5 mg/kg, IV) is the induction drug of choice for patients that have

cardiovascular disease or arrhythmias (except A-V dissociation).  There have been reports of

hemolysis in cats after etomidate injection.  Weigh the risk of hemolysis  against the benefit of

cardiovascular stability in making  a decision.  A premedicant (eg, butorphanol IV, SC, IM;

diazepam or midazolam IV)  should be administered  prior to etomidate to decrease the side

effects of injection of etomidate.  Etomidate is non-cumulative, maintains cardiac output and is

not arrhythmogenic.  Etomidate has protective effects for decreasing intracranial pressure

(vasoconstriction) and effects on metabolic oxygen requirements similar to thiopental.  Side

effects include transient adrenal suppression, activation of seizure foci, pain on injection,

vomiting, and myoclonus.  Ketamine (6 mg/kg IV) and diazepam (0.3 mg/kg) mixed IV to effect continue to be used as long as there are no contraindications. The largest being  renal failure since ketamine is cleared

unchanged by the kidneys in cats. Any increase in intracranial or intraocular pressure, seizure

history, mitral regurgitation, or sympathetic exhaustion would limit the usefulness of the

combination.  Anesthesia is generally maintained with isoflurane or sevoflurane in oxygen, since they

maintain contractility better than  halothane and are not  arrhythmogenic.  Very little isoflurane  or

sevoflurane is metabolized, and the insolubility of the inhalants allows for a speedier  induction

and recovery.  In selected cases (MRI, airway exam) propofol infusion (0.4 mg/kg/min, IV)  may

be used for anesthetic maintenance;  however, oxygen should be available and, if painful

procedures are done, an analgesic should be included.  Mannitol is particularly useful  in geriatric cats with chronic renal failure (and normal hearts) to ensure diuresis. Make sure the cats are well-hydrated.


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