Primary goal when anesthetizing critically ill patient:
Keep inhalant concentration as low as possible.
Anesthetic agents with most carfiovascular and respiratory depressants
Inhalant anesthetics
Balanced Anesthesia (and 4 things it achieves):
Concurrent administration of multiple drugs from different classes to achieve:
1. Hypnosis
2. Amnesia
3. Analgesia
4. Muscle Relaxation
Neuroleptanalgesia (and 6 things it achieves)
Opioid + Sedative/tranquilizer
Works synergistically to:
1. Facilitate handling
2. Decrease stress
3. Decrease induction dose
4. Decrease inhalant concentration
5. Assist with smooth recovery
6. Provides preemptive analgesia
Preemptive analgesia
Administering analgesic before painful stimulus
Preemptive analgesia prevents:
Central and peripheral sensitization, which can cause an exaggerated response to pain
Induction agents produce a ______________
Smooth, rapid transition to general anesthesia
Induction agents that can go IM (2)
1. Ketamine
2. Alfaxolone
Maintenance period:
Usually involves inhalant agents
May use injectable for short term procedures
May also use total intravenous anesthesia (TIVA)
Why is multimodal approach to anesthesia the best?
Ensures nociceptive stimulation is prevented by using drugs that work at different locations along pain pathway.
Nociceptive pain
Pain caused by physical damage to body
NSAIDs are best used for treatment of ____________
Acute, mild-mod. pain associated with inflammation
Primary mechanism of action for NSAIDs
Blocking prostaglandin formation via inhibition of cyclooxygenase enzymes (COX-1 and COX-2) in arachidonic acid cascade
COX-1 Function
involved with normal hemostatic functions (renal bloodflow, GI cytoprotective mechanisms, platelet aggregation)
COX-2 Function
Activated by inflammatory cells, triggers production of inflammatory prostaglandins that contribute to peripheral sensitization and GI ulceration. Serves beneficial homeostatic role.
NSAIDs approved in dogs (7):
1. Carprofen - Rimadyl
2. Deracoxib - Deramaxx
3. Etodolac - Lodine
4. Firocoxib - Previcox
5. Meloxicam - Metacam
6. Tepoxalin - Zubrin
7. Mavacoxib - Trocoxil
NSAIDs have more selectivity for COX-1/COX-2inhibition. Some have weak COX-1/COX-2 inhibition (which 2?)
COX-2
COX-1
Carprofen, Etodolac
Tepoxalin unique in that it inhibits what?
COX and Lipoxygenase (LOX)
Lipoxygenase
Responsible for formation of leukotrienes that further precipitate inflammatory cascade
Which 2 NSAIDs come in injectable and oral, and what are the forms of the rest?
Carprofen and Meloxicam injectable and oral, others strictly oral
Why don't cats metabolize NSAIDs
Deficiency in glucuronyl transferase enzymes
NSAIDs approved in cats (2)
Meloxicam for 1 time use
Robenacoxib for maximum 3 days
Most widely reported NSAID side effects
GI toxicity:
Gastritis
V/D
GI ulceration
GI perforation in severe cases
When are side effects to NSAIDs most likely to occur
Inappropriate dosing or use with other NSAIDs or corticosteroids
Why is hydration status important to consider when administering NSAIDs pre-op?
Only administer if well hydrated.
Prostaglandins play vital role in regulation of normal renal function by maintaining renal blood flow
Why should NSAID use be avoided with hypoabluminemia
NSAIDs are highly protein bound
Why are opioids called the juice of the poppy
Poppy source of 20 distinct alkaloids of opium
Mechanism of action for opioids:
Bind to opioid receptors located at presynaptic and postsynaptic sites in the CNS (brainstem and spinal cord) and peripheral tissues.
Block transduction in physical tissues
Dampen modulation and perception
Transduction
Conversion of physical energy into electrical energy by a nociceptor
Modulation
Amplification or suppression of nerve signals in the spinal cord
Where does perception of pain occur
Occurs in dorsal horn of spinal cord
3 types of opioid receptors
Mu (Mu-1 and Mu-2)
Kappa
Delta
Pure agonists
Stimulate opioid receptors
Predominantly mu receptors ("Pure Mu Agonists")
Agonists/antagonists
Block one type of receptor while stimulating another
Partial agonists
Bind to receptor, less efficacious compared to pure agonist
Pure antagonist
Attach to receptor but do not activate it (reversal agents)
Dogs often sedate/excited when administered opioids and why
Opioids may cause minor sedation due to CNS depression
Most prominent canine conditions to display sedation when opioids administered
Pediatric
Geriatric
Debilitated
Cats may show sedation/excitement when opioids used under what circumstances and how to avoid
May show excitement when opioids used alone or at high doses due to CNS stimulation.
Reduced by co-administration of sedative
List of pure agonists opioids (6)
1. Morphine
2. Hydromorphone
3. Oxymorphone
4. Meperidine
5. Methadone
6. Fentanyl
Best opioid option for treatment and prevention of surgical pain
Pure agonists
Somatic pain
Skin, tissue, and muscle
Pure agonists are effective against what types of pain
Visceral and Somatic pain
Effects of pure agonist opioids are ___________
Cumulative
^ dose/ ^ frequency = ^ analgesia
Common side effects of pure agonist opioids (4)
1. Vomiting
2. Dose-dependent decrease in respiration (rarely significant unless high dose)
3. Dose dependent decrease in HR and BP (except meperidine)
4. Dysphoria during recovery if given alone or pt in a lot of pain
Pure agonists most likely to cause vomiting in order (3)
1. Morphine
2. Oxymorphone
3. Hydromorphone
Pure agonists lease likely to cause vomiting in order (2)
1. Methadone
2. Meperidine
If vomiting is contraindicated, when should pure agonists be administered
After induction, as pt will not vomit if induced to general anesthesia
When is vomiting less likely when administering pure agonists
Less likely if pt already in pain or if drug is given IV
Meperidine effect on HR
Tachycardia
What breeds are more prone to dysphoria during recovery if administered pure agonist opioid
Arctic breeds
What can help with dysphoria caused by pure agonist opioids during recovery
Butorphanol can also act as partial reversal as long as expecting lower pain levels
What medications can cause hyperthermia in cats
1. Hydromorphone during recovery
2. Morphine
3. Butorphanol
4. Buprenorphine
When should reversal with Naloxone be considered for cats experiencing drug induced hyperthermia?
In severe cases with an elevated temperature lasting longer than 4-6 hours
Morphine active metabolite
Morphine-6-glucuronide
Metabolized to this by glucuronidation
Longer duration of action than oxy or hydro
Why is morphine less effective in cats?
Cats have decreased ability to metabolize through glucuronidation
How potent is meperidine when compared to morphine
Meperidine is 1/8 as potent as morphine
Pure agonist opioid with shortest duration of action
Meperidine
Does meperidine cause sedation in healthy animals?
Only causes mild sedation when given alone to healthy animals
What may happen if morphine and meperidine administered rapidly IV?
May cause histamine release
Avoid in patients with preexisting hypotension
Low dose morphine CRI unlikely to cause histamine release
What drugs should meperidine and methadone not be given with and why
Monoamine oxidase inhibitors (MAOI) or tricyclic antidepressants
Both serotonin reuptake inhibitors
When combined, may cause serotonin toxicity
Potentially life threatening
Why is Methadone beneficial for treatment and prevention of "wind up" pain?
NMDA Receptor antagonist
List of Partial Mu Agonist
Buprenorphine
What receptors does buprenorphine have effect on
Partial agonist at mu receptor
Little to no effect on kappa receptor
Potency of buprenorphine compared to morphine
Buprenorphine 30 times more potent than morphine
Potency
refers to amount of drug required in order to achieve its maximum effect. Does NOT imply anything about analgesic efficacy
Side effects and precautions for buprenorphine
1. Slight respiratory depression
2. Unlikely to cause vomiting
Onset of action time for buprenorphine
Slow onset of action, peak effect occurring ~30-45 mins post IV/IM administration
Duration of action buprenorphine
Dose dependent (6-8 hours)
Higher dose = longer duration of action
"Ceiling effect" buprenorphine
After repeated doses, maximal analgesic efficacy reaches plateau. No further increase in analgesia even though duration of action is prolonged
What kind of pain is buprenorphine best for?
Best for mild-moderate pain
Can buprenorphine be used transmucosal in dogs?
Not recommended
Acidic saliva decrease bioavailability to 30-50%
Can buprenorphine be used with pure agonists?
Should be avoided, buprenorphine has very high affinity for mu receptors
May competitively inhibit pure mu agonist from binding, may need to give higher doses of pure mu agonist
Giving buprenorphine afterwards can potentially act as a "reversal" agent
Agonist/Antagonist drugs
1. Butorphanol
2. Nalbuphine
What receptors do Agonist/Antagonists stimulate?
Stimulate Kappa receptor
Antagonize Mu receptor
What pain are Agonist/Antagonists good at treating
Effective at treating mild pain
Good for visceral pain, not for somatic pain
Do Agonist/Antagonist provide sedation?
Mild sedation in dogs and limited sedation in cats when administered alone
Synergistic and profound sedation when combined with sedatives or tranquilizers
Side effects and precautions for Agonist/Antagonists
1. Respiratory depression is minimal
2. Little direc effect on cardiovascular system
3. Vomiting not commonly seen
"Sequential analgesia" with Agonist/Antagonists
Can be used as reversal agents for pure agonists to partially reverse respiratory depression and sedation while maintaining some analgesic effect
Duration of action for Agonist/Antagonists
Short (30 min - 1 hour)
"Ceiling effect" with Agonist/Antagonists
Increase dose or repeated doses prolongs duration of action without increasing intensity of analgesia or sedation
List of opioid antagonists
1. Naloxone
2. Nalmefene
What do opioid antagonists do?
Completely reverse the adverse cardiopulmonary, sedation, and analgesic effects of opioids.
Should only be considered with absolute opioid overdose
Why is a partial reversal of an opioid not recommended?
Difficult to assess when effects of respiratory depression are decreased while some of analgesic effects are still present
Why should you use caution when reversing an opioid?
Acute awareness of pain can lead to sympathetic stimulation:
1. Catecholamine release
2. Cardiac arrhythmias
3. Hypertension
4. Detah
How to administer opioid antagonist
Dilute in saline, titrate IV slowly to effect over 5-10 mins
Naloxone onset time
1-2 mins IV
5 mins IM
Naloxone duration of action
30-60 mins
Additional doses may be necessary for complete reversal to avoid re-narcotization
What opioid may be hard to fully reverse?
Buprenorphine, strong affinity for mu receptors
Nalmefene onset time
1-2 mins IV
5 mins IM
Nalmefene duration of action
1-2 hours
Types of sedatives/tranquilizers
1. Phenothiazines
2. Benzodiazepines
3. Alpha-2 Agonists
Types of opioids
1. Pure agonists
2. Partial mu agonist
3. Agonist/Antagonist
4. Opioid antagonist
Types of induction agents
1. Barbiturates
2. Dissociatives
3. Propofol
4. Etomidate
5. Alfaxalone
Most commonly used phenothiazine for sedation
Acepromazine
Other properties besides sedative effects of acepromazine
1. Antiemetic
2. Antihistamine
3. Antiarrhythmic
Side effects and precautions of Ace
Does not cause significant respiratory or cardiac depression at clinically significant doses
Causes slight decrease in GI motility
No analgesia
No reversal agent
Causes peripheral vasodilation that can lead to hypotension
Inhibits platelet aggregation
May lower seizure threshold
Some european line boxers may be more sensitive, prone to fainting and sudden collapse
Routes of administration for Ace
IV
IM
SG
Acepromazine duration of action
6-8 hours
Acepromazine with respiratory distress patients
Low doses of ace may be beneficial
Fort Dodge dose for ace for sedation when used alone
0.5 - 1.1 mg/kg
*Manufacturer dose much higher than what is actually required for premedication
Boehringer Ingelheim dose for ace for sedation when used alone
Dog: 0.1 - 0.2 mg/kg
Cat: 0.2 - 0.4 mg/kg
Premedication dose for ace when combined with other drugs such as an opioid
0.01 - 0.05 mg/kg
Why can ace cause hypotension
Causes blockade of alpha-1 adrenergic receptors
Causes peripheral vasodilation
Effect dose dependent - usually only at manufacturer dose
What patients should Ace be avoided in due to platelets
Thrombocytopenia or clotting disorders due to platelet aggregation
Platelet aggregation
The clumping together of platelets in the blood (thrombus formation)
List of benzodiazepines
1. Diazepam
2. Midazolam
Benzodiazepine properties
Anxiolytic
Mild sedation
Skeletal muscle relaxation
Anxiolytic properties
Anti-anxiety
Drugs used as first line anticonvulsant
Benzodiazepines
Precautions and side effects of benzodiazepines
Minimal effect on cardiovascular and respiratory systems at normal doses
Provide no analgesia
No reliable sedation in young, healthy animals
Highly protein bound (90%) - use with caution with hypoalbuminemia or other highly protein bound drugs (NSAIDs)
Though to worsen clinical signs of hepatic encephalopathy
Benzodiazepines are best at causing sedation in what animals
Pediatrics (<8 weeks old)
Geriatrics
Critically ill
Debilitated animals
What can benzodiazepines cause in young, healthy animals and when is this more likely
Hyperexcitability
Difficulty handling
Aggression
If delivered alone or even with opioid
Why is IM/SQ administration of Diazepam not advised
Diazepam insoluble in water, prepared in propylene glycol
Causes pain when delivered IM/SQ and unreliable absorption
Why must Diazepam be administered slowly IV
Rapid injection can cause dysrhythmias and thrombophlebitis due to propylene glycol carrier
What medications will cause precipitate to form with Diazepam?
Atropine
Acepromazine
Barbiturates
Opioids
What medication can be mixed with Diazepam?
Ketamine
How long can Diazepam be stored in plastic?
Absorbs into plastic and decreases active drug concentration in solutions. Do not store in plastic longer than 2 hours
Midazolam route of administration
IV
IM
SQ
Is midazolam compatible with other drugs?
Yes
Is Diazepam compatible with other drugs?
Incompatible with most drugs and solutions
Midazolam is _________ soluble
Water soluble
Reversal agent for benzodiazepines
Flumazenil
Competitive blocker of benzodiazepines at the GABA receptors located in the CNS.
Antagonizes the sedative and amnesic effects
Not commonly used due to cost
How to administer Flumazenil
Give IV and titrate
Effects usually noted within 2 minutes
List of Alpha-2 Agonists
1. Xylazine
2. Medetomidine
3. Dexmedetomidine
Dexmedetomidine commonly used in ___________
USA
Medetomidine still available in _________
Canada
Xylazine commonly used in what type of animals?
Large animals
Main effects of alpha-2 agonists
Profound sedation and muscle relaxation
Do alpha-2 agonists provide analgesia?
Yes, but effects are shorter duration than the sedative effects
Precautions and side effects of alpha-2 agonists
Minimal effect on respiratory system
Biphasic effect on blood pressure
Significant bradycardia (HR decreases by 50% of normal resting rate)
Inhibit antidiuretic hormone (ADH) and insulin release
Heavily sedated dogs may respond with aggression to touch or stimulus
Increase dose will increase duration of action but level of sedation will reach a plateau
alpha-2 agonists biphasic effect on blood pressure
1. Initial activation of peripheral post-synaptic alpha-2 receptors results in vasoconstriction and period of hypertension
2. After central and peripheral pre-synaptic alpha-2 receptors activated, results in sustained decrease in BP due to vasodilation (blocks norepinephrine)
Is bradycardia concerning with alpha-2 agonists
Normal physiological response, no need to treat if adequate blood pressure
Decrease in sympathetic drive allows vagal tone to predominate
Baroreceptor reflex responds to the initial hypertension with reflex bradycardia
Decrease in cardiac output results due to decreased HR, but studies show organ perfusion is still adequate
What does inhibition of ADH and insulin release cause with alpha-2 agonists
Causes diuresis and transitory hyperglycemia
alpha-2 agonists cause what reduction of induction and inhalant concentrations
Can cause up to 80% reduction in induction agents
50% reduction in inhalant concentration
Micro-doses intra-op can help maintain steady state of anesthesia while keeping inhalant low
What causes most predictable sedation?
C. Alpha-2 agonists
When is sedation unlikely to occur with alpha-2 agonists
If pt. is frightened, stressed, or excited prior to or after administration
Leave in a quiet environment 20 mins pre and post-administration to allow for maximum affect
How long should patients be left in a quiet environment for maximum sedative effect of alpha-2 agonists
20 minutes before and after administration
alpha-2 agonists reversal agent
Atipamezole
Competitively binds to and inhibits alpha-2 receptors and reverses both sedative and analgesic effects
How should atipamezole be administered
Give IM
Can be diluted in saline and titrated to effect IV in emergency
List of anticholinergics
1. Atropine
2. Glycopyrrolate
Anticholinergic mechanism of action
Block the action of acetylcholine at muscarinic receptors of parasympathetic nervous system
Anticholinergics treat:
1. Sinus bradycardia
2. Atrioventricular block
3. Sinoatrial arrest
When will Anticholinergics increase HR with bradycardia
Only when bradycardia due to vagal stimulation. Bradycardia due to hypothermia will not respond to anticholinergics
Anticholinergic of choice during sinoatrial arrest
Atropine, fastest onset time
What Anticholinergic has fewer tendencies to cause severe tachycardia and cardiac arrhythmias
Glycopyrrolate
Why should Anticholinergics only be used in premed if deemed necessary?
Tachycardia can be just as detrimental to heart. Can lead to:
1. Increased cardiac workload
2. Increased myocardial 02 consumption
3. Decreased cardiac output and 02 delivery (due to decreased filling time)
4. Increased potential for cardiac arrhythmias
What patients require Anticholinergics in their premeds?
Pediatric patients <12 weeks
Why do pediatrics <12 weeks require Anticholinergics in their pre-meds?
Rely on HR rather than contractility to maintain cardiac output
Cases where Anticholinergics should be considered for a pre-med
Brachycephalic patients
Procedures involving head/neck or eyes
Patients with pre-existing bradycardia
Precautions and side effects for Anticholinergics
Suppresses salivation, glycopyrrolate more so, but neither prevents it
Secretions present increase in viscosity so increased risk of mucous plug in endotracheal tube (especially in small dogs and cats)
Both capable of producing arrhythmias (arrhythmogenic) where initial arrhythmia worsens before the increase in HR
Arrhythmogenic
Drug capable of producing arrhythmias
List of dissociatives
1. Ketamine
2. Telazol
What else are dissociatives referred as
cyclohexamines
What pain are dissociatives good for
Good for somatic analgesia
Block central neuronal hypersensitization ("wind up") in dorsal horn of spinal cord
Should not be used as sole analgesic agent, contribute good multimodal pain management in CRI
dissociatives mechanism of action
Do not produce "true" anesthetic state
Appear to cause dissociation between thalamus and limbic systems of brain
Sub-anesthetic dose act as N-methyl-D-aspartate (NMDA) antagonists
Which dissociative has longer duration of action
Telazol
Telazol made up of:
dissociative agent tiletamine and benzodiazepine zolazepam
Side effects and precautions of dissociatives
Primary effect on cardiovascular system is depression of myocardial function
Secondary stimulation of sympathetic nervous system (indirect effect)
Why should ketamine never be administered alone?
Can produce:
Muscle and limb rigidity
Increased intracranial pressure
Increased intra-ocular pressure
Potential seizures due to CNS stimulation
What is ketamine typically administered with?
Benzodiazepine such as diazepam
What can secondary stimulation of sympathetic nervous system by dissociatives lead to?