Injectable anesthetic agent

Question 1

General anaesthesia

Answer 1

State of reversible unconsciousness produced by general anaesthetic agents
Central acting
Coma like state
Absence of pain sensation over the entire body; not aware of stimulus, amnesia
Varying degrees of muscle relaxation, immobility
Always see changes in CV and pulmonary function
Temporary, only so long as the drug is active

Question 2

The 4 stages of general anesthesia

Answer 2

Stage 1- voluntary excitement/conscious fear response
Stage 2- involuntary (unconscious) excitement
Stage 3- unconsciousness (surgical anesthesia)
Plane 1- light unconsciousness (goal of induction)
Plane 2- moderate unconsciousness (surgical plane)
Plane 3- deep unconsciousness (early overdose)
Stage 4- anesthetic overdose

Question 3

stage 1 of anesthesia causes

Answer 3

Voluntary excitement; conscious fear response
Still conscious, but losing consciousness
Fear, excitement; fight or flight
Disorientation, struggling
Increased HR, increased RR, increased BP
Urination, defecation, panting and/or breath-holding

Question 4

Stage 2 of anesthesia causes

Answer 4

Involuntary (unconscious) excitement
Unconscious fight or flight
Loss of voluntary control
Twitching, paddling, moaning, tremors, rigid limbs; dilated pupils
Irregular breathing
Towards end of stage 2, muscular relax, decreased reflexes, slowing down HR/RR

Question 5

What is the goal for anesthetic induction

Answer 5

Goal during induction is to get the patient through stages 1 and 2 as quickly as possible to minimize their stress

Question 6

Stage 3 of anesthesia causes

Answer 6

Unconsciousness
Surgical plane of anesthesia
Decreased cardiopulmonary function and decreased response to stimulus
Decreased sympathetic functions
Breathing is regular
There are 3 planes of unconsciousness within stage 3

Question 7

Stage 3 plane 1 of anesthesia is

Answer 7

Light surgical plane
Light unconsciousness
Decreased muscle tone; decreased reflexes; decreased sensation, but still react to painful stimulus (HR,RR< and BP will increase if painful stimulus applied)
Movement is possible
This is the goal of induction
Can intubate and prep patient
Inadequate for surgery

Question 8

Stage 3 plane 2 of anesthesia is

Answer 8

Moderate unconsciousness
Surgical plane
Adequate, ideal degree of unconsciousness for surgery
Depressed CV function and respiration
Vitals are steady and stable
Minimal muscle tone, no reflexes, no reaction to most painful procedures
If pulling on viscera e.g. ovarian ligament may still see transient increase in HR/RR/BP

Question 9

Stage 3 plane 3 of anesthesia is

Answer 9

Deep unconsciousness (aka early overdose)
Extensive CNS depression
Significant CV, resp depression
NO muscle tone, no reflexes; limp
Early warning is that the patient is no longer stable. WARNING: TOO MUCH ANESTHETIC!
May need to manually support ventilation; will need to support BP

Question 10

STage 4 of anesthesia is

Answer 10

Anesthetic overdose
Brainstem paralysis
CV, pulmonary collapse (aka shock)
Initially will see fight or flight response (dilated pupils, increase HR/RR); rapidly followed by shutting down of cardiovascular and resp functions (rapid increased in HR,RR,BP, mm go white)
Death will ensure in 1-5 mins if you do nothing
STOP ANESTHETIC, STRAT CPR

Question 11

3 parts of preforming GA

Answer 11

Induction
Maintenance
Recovery

Question 12

Induction part of GA

Answer 12

The process where patients move through stages 1 and 2; enter stage 3
Patient moves from conscious to unconscious
Induction should always be rapid as stages 1 and 2 are NOT nice (for patient or handler)
Induction is typically with a general anesthetic
Injectable GA provide the fastest induction; can be so quick that stages 1 and 2 are never noticed
Stage 1 can also be achieved by overdosing on a sedative. Recall that patient is still conscious in stage 1

Question 13

Maintenance for GA

Answer 13

Where the patient is consistent at stage 3
Consistent depth of unconsciousness; CNS depression
Consistent CV and resp function
If painful procedures are being performed; then the patient should be in plane 2
Most commonly, patients are maintained with an inhalant anesthetic
Occasions where maintenance is with an injectable anesthetic

Question 14

Recovery of GA

Answer 14

After the anesthetic is turned off or no longer being administered, the patient will go through the stages in reverse order
Like induction, a slow recovery can be rough
Smooth recoveries are typically fast, but controlled
The patient returns to a state of consciousness
Typically, use return of vitals to pre-anesthetic norms and sternal recumbency as end of recovery period

Question 15

Knowing drugs and monitoring

Answer 15

Anaesthetic accidents are devastating
Can result in permanent injury, death, loss of licence, lawsuit
Majority can be prevented by
Knowing your drugs
Proper dosing and administration
Appropriate monitoring (know norms)
Accurate communication b/w vet and tech
Using highest standards of care
Always keep meticulous records

Question 16

Injectable GA

Answer 16

Drugs given by IV route
Centrally acting depressants (all of them)
Must reach the brain to work properly
Designed to cross the BBB; usually very lipophilic
Used as part of balanced anaesthesia, with or without an inhalant anesthetics
Require inactivation/elimination by the liver/kidneys

Question 17

Why are Injectable anesthetic drugs the preferred method

Answer 17

Prefered for induction in all species (over gas induction)
Most rapid onset of stage III
Considered the standard in all medium to large dogs and LA
Exception is small exotics, cats and very small dogs when inducing with an inhalant anaesthetic may be considered acceptable in specific situations
May be single drug or combination of drugs
Always given IV to effect
Except in large animals where calculated dose should be given ( a LA that is not fully anaesthetised is dangerous)

Question 18

Limitations in injectable anesthetics

Answer 18

Causes CNS, CV and resp depression
Always a risk of debilitating or fatal overdose
Must monitor HR, ventilation and BP
Do not provide (sufficient) analgesia
Must use with analgesics for painful procedures
Do not provide muscle relaxation
Combine with muscle relaxants, inhalant anesthetics
Very low TI; no error for mistakes
Must dose accurately for the individual patient
Cannot be reversed or removed
Supportive care only of overdose or adverse reaction
Have a longer recovery period than inhalants

Question 19

Why do IV anesthetics cause a longer recovery time

Answer 19

Require liver metabolism and/or elimination
Longer recovery periods have more excitement and/or hallucinations. Therefore, not preferred for recovery (when an inhalant is available)
In most cases, injectable anesthetic is used for induction; inhalant anaesthetic is used for maintenance and recovery

Question 20

Using injectable anaesthetics

Answer 20

Always dose for lean body weight
Always administer “to effect” IV (SA)
Do not administer too rapidly
Giving too fast can cause arrhythmias and induction apnea (breath holding)
Wait 15-90 sec after each increment
Always use a catheter
Can give to effect easier
Ensures venous access since drugs will cause some degree of hypotension
Can use alone for short procedures
Induction is followed by 5-20 min of GA
Check and double check doses
Low TI, cannot reverse

Question 21

How to administer IV anesthetics to effect

Answer 21

Calculate and draw up the full dose for the patient
Using an IV catheter, only give ¼ - ½ of total dose→flush→watch for effect. If more drug is needed, give another ¼ of total dose→ flush→ watch for effect,…Repeat until animal is in stage 3, then stop
Purpose: only give as much drug is required; decreased risk of overdose

Question 22

Total intravenous anaesthesia (TIVA)

Answer 22

Method where only injectable anesthetic drug(s) are used to maintain general anaesthesia for any duration of time but typically for procedures <60 minutes
Including induction and maintenance
I.e., no inhalant is used
Drug is by IV infusion (ex. CRI)
Currently used in equine field work (e.g. triple drip, more recently medetomidine+ketamine+midazolam) and occasionally in SA

Question 23

Examples of Injectable anaesthetic drugs

Answer 23

Barbiturates- thiopental, pentobarbital
Dissociative anaesthetics- ketamine
Guaifenesin
Propofol
Alfaxalone
Others include
Synthetic opioids- fentanyl, sufentanil, etorphine (distinct as these provide analgesia and are reversible)- wildlife
Etomidate

Question 24

Barbituates are

Answer 24

Barbituates were commonly used as general anaesthetics, but due to development of newer injectable agents and inhalants and the loss of availability of Thiopental, they are now only used for specific inductions
GABA agonists

Question 25

How do barbituates work

Answer 25

GABA agonists Thiopental- no longer available Phenobarbital→ anticonvulsant; not useful for anesthesia Phenobarbital sodium (Euhtanyl, Euthanosol)--> humane euthanasia Controlled drug DO NOT dilute for use as seizure control or anesthesia!!! Contain toxic preservations which cause red blood cell hemolysis Dyes may be added when opened to prevent accidental misuse

Question 26

Dissociative anesthetics: cause

Answer 26

Unlike most general anesthetics which cause general CNS depression, dissociative anaesthetics cause disruption of nerve transmission in some parts of the brain and select stimulation in others Inhibit NMDA receptors in the CNS that are responsible for windup= an exaggerated response to low intensity pain Provide some somatic analgesia but no visceral analgesic therefore should not be the only analgesic provided “Dissociative anaesthesia” creates distinctive trancelike state ***No reversal

Question 27

Ketamine is

Answer 27

Vetalar, Ketaset Controlled drug Phencyclidine derivative (PCP, angel dust, date-rape drug) Complex mechanism, Disrupts nerve transmission in some parts of brain Stimulates other parts of the brain

Question 28

Physiological effects of ketamine

Answer 28

Immobility Muscle tone is unchanged or rigid Dissociative anesthesia Out of body experience? Somewhat aware but immobilized Temporary to long term amnesia Moderate, brief control of somatic pain (pain originating form muscles, skin, bone) Less effects on cardiovascular and resp functions than other anesthetic-apneustic breathing pattern Note: reflexes remain intact and cats have centrally located dilated pupils

Question 29

Ketamine is metabolized where and when to avoid

Answer 29

Ketamine is metabolized by the liver in dogs; but excreted in active form in all other species. Recovery occurs due to rapid redistribution of the drug out of the brain. Therefore, avoid or use caution if liver function is compromised in dogs or kidney disease in others. Prolongs recovery and/or increases toxicity No reversal agent

Question 30

Contraindications of ketamine

Answer 30

Seizure Brain trauma Neurotoxins (strychnine, street drugs, insecticides)

Question 31

Adverse effects of ketamine:

Answer 31

Increased response to sensory stimuli during recovery May cause seizures and/or convulsions in dogs if given alone - avoid using alone if Hx or risk of seizure Behavioural change may last for a few days Abnormal nystagmus in cats Pain if given IM – therefore ideally use IV

Question 32

Indications of ketamine

Answer 32

Chemical restraint-only time it is used on its own e.g. sprayed orally in difficult cats Induction or general anesthesia when combined with other drugs Has a fairly high TI compared to the other injectable anesthetic

Question 33

Using ketamine

Answer 33

IV use (only) in all species, IM painful Give to effect Onset of action 30-90 sec Duration 10-20 min Multiple routes in cats when used for chemical restraint IM (will be painful) PO (tastes horrific) Duration: 10 min immobility

Question 34

Why is ketamine not used alone

Answer 34

still feel pain, still aware, short duration

Question 35

When do you use ketamine in equine

Answer 35

Short field anaesthesia equine Pre sedate with an alpha 2+an opioid (often butorphanol) Once sedated induce with ketamine alone or ket/val

Question 36

KetVal is

Answer 36

Mixture of ketamine+diazepam Diazepam can be replaced with midazolam in older or sick animals Induction agent Commonly used Induction of dogs, cats, calves, foals, horses Mix in same syringe; will diazepam will NOT precipitate with ketamine- only exception currently

Question 37

How to give ketval

Answer 37

Give IV to effect (SA not Eq); can take up to 1 min to see effects. Allows for 5-20 min GA

Question 38

Advantages of ketval

Answer 38

Rapid induction Provides true unconsciousness Less cardiovascular and rep depression compared to other general anesthetics (induction agents) Diazepam provides very good muscle relaxation and loss of reflexes that would be seen with ketamine alone Some analgesia (due to ketamine) BUT, router recoveries in cats than other induction agents

Question 39

Kitty magic is and provides what

Answer 39

Ketamine in combination with dexmedetomidine (xylazine) and an opioid Produces a state of sedation to anesthesia depending on dose (neuroleptanalgesia) Can be used for minor surgical procedures Provide supplemental oxygen where possible Should always lubricate the eyes to prevent drying of the cornea (as with any general anaesthetic) Similar combination can also be used in dogs

Question 40

Guaifenesin is and used for

Answer 40

Not controlled Only used in LA (for balanced anaesthesia) On its own, it is a centrally acting skeletal muscle relaxant at recommended dose Acts on CNS; blocks motor pathways Exact mechanism of action is unknown Some sedative properties NOT AN ANESTHETIC ON ITS OWN

Question 41

Guaifenesin clinical indications

Answer 41

When used on own Muscle relaxant Expectorant- loosens airway secretions os easier to cough Very mild sedation As part of balanced anesthesia in LA Increases the CNS depressant effects of other premeds and anesthetic drugs Decreases dose of other drugs required Relaxes pharyngeal and laryngeal muscles so easier to intubate Skeletal muscle relaxation during surgery Smooths induction and recovery

Question 42

Triple drip is and used for

Answer 42

(Ketamine + xylazine + guaifenesin) Horses, cattle, sheep Significantly lower xylazine dose in cattle/sheep

Question 42

Adverse effects of guaifenesin

Answer 42

Minimal CV and respiratory effects on own at therapeutic dose If 3-4x overdose, will cause muscle rigidity and cardiorespiratory arrest Perivascular injection will cause pain and tissue damage Always use a catheter Inflammation to the veins at injection site – must flush Possible hemolysis if not diluted

Question 43

Indications of triple drip

Answer 43

Indications infusion to achieve: Heavy sedation IV induction, to be followed by a gas anesthetic TIVA (up to 1 hr) for equine field work Good CV and respiratory stability compared to other injectable anesthetics; very smooth induction and recovery compared to most injectable GAs

Question 44

Propofol (Diprivan®, Propoflo®) does what

Answer 44

Mechanism of action: GABA receptor agonist (GABA inhibits the CNS) CNS depression Good muscle relaxation NO analgesia Max duration of action is approximately 10 min depending on dose; can be shorter Considered Ultra short-acting Not controlled- However, potential for abuse exists – some clinics keep bottles locked up. No Reversal

Question 45

Identifying propofol

Answer 45

Very distinct looking-MILKY This is the only “milky” emulsion that is given IV Contains egg and soy so allergies may be an issue

Question 46

Storing and handling of propofol

Answer 46

Emulsion containing soy and egg Ideal medium for bacteria growth Use aseptic technique when handling bottle Shake before use Store b/w 4-25*C, don't freeze Label advises to discard “after procedure”, ~6 hours Long term storage increases risk of bacterial contamination therefore patient risk of septicemia if used Most practices use for the day or up to a max of 24 hours and refrigerate it after opening

Question 47

Pharmacokinetics of propofol

Answer 47

Administered IV (rapid loss of consciousness) Unbound drug is very lipophilic The brain has high volume blood flow and high fat content; so drug distributes to and enters brain rapidly Crosses the BBB and produces induction in <30 sec **Drug is only active while in the brain Drug leaves the brain There is active removal of drug by the MDR1 pump Also moves out of area –passive diffusion Drug redistributes to fat stores Drugs moves from fat to liver for metabolism Metabolite is eliminated by kidneys in urine In dogs there is also some biliary excretion with some enterohepatic recirculation

Question 48

How does propofol move to fat stores

Answer 48

Moves towards fatty tissues with lower drug concentration (adipose, SQ fat) Watch very thin patients Drug is not active when in fat Patient will wake as drug leaves the brain (~10-15 min) even though drug is still in body (long elimination half life) Despite long half life there is little accumulation in most species

Question 49

How doe propofol move from fat to liver

Answer 49

Metabolized to water soluble inactive metabolites by glucuronidation (careful cats*) and CYP450 enzymes Rapid metabolism in dogs therefore a good choice for induction for C-section; not same for cats

Question 50

Clinical use of propofol

Answer 50

Commonly used SA, exotics, neonates of all species Limitation is cost, $$$ Also limited by concentration/volume in horses Induction – can give as IV bolus - better to give or titrate to effect Onset – 20-40 seconds Maintenance (TIVA) up to 20 minutes Anti-convulsant (stop seizures) Can give as IV bolus for emergency treatment of seizure or CRI for status epilepticus

Question 51

Adverse effects and warnings of propofol

Answer 51

Cardiovascular and respiratory depression Induction apnea causing cyanosis Stop breathing (minutes); consistently occurs if given too fast Offset risk by pre-oxygenating prior to inducing Less likely if giving slowly to effect vs bolus Excitement + twitching/tremors/paddling + opisthotonus + abnormal nystagmus Occurs after induction in 12% of dogs and cats Can look like a seizure or focal seizure, but is not a true seizure More likely to occur if using without pre-med Repeated used in cats over several days can cause hemolysis and possible CNS (mentation) effects Drug remains in body (outside CNS) longer because of poor glucuronyl transferase metabolism Risk of bacterial sepsis if not handled properly

Question 52

Induction using propofol

Answer 52

Pre-oxygenate patient due to risk of induction apnea Give flow-by 100% oxygen for 3 min prior to induction Give IV to effect Induction is rapid and smooth Can give repeated small boluses for maintenance-doesn’t accumulate Managing induction apnea: Monitor C02/02 levels closely Most spontaneously resume breathing may take 1-2 minutes Provide O2 (bag patient) IF needed.

Question 53

Recovery from propofol

Answer 53

Recovery is rapid and smooth Complete recovery in 20-30 min

Question 54

propofol with c-sections

Answer 54

One of the preferred anesthetic for c-section in dogs. Can use alone IV for rapid induction with no other premed Drug will enter the fetus Must wait 10-20 minutes after administration before detaching placenta Fetal liver is still immature and less able to metabolise drug Allows drug to leave fetus and be metabolized by the maternal liver

Question 55

Alfaxalone /Alfaxan-CD RTUTM is

Answer 55

Ultra short-acting injectable IV anaesthetic drug Also a GABA receptor agonist Provides rapid, smooth induction and good muscle relaxation with rapid recovery through redistribution (also rapid metabolism) Slow IV to effect Poor analgesia Noncontrolled No reversal

Question 56

Why is alfaxolone a good induction and how long does it work

Answer 56

Lack of accumulation (even in cats) makes it ideal for infusions Dogs and cats. LA use is limited (again mainly due to concentration issues) Duration of action = 5-10 min in dogs, 15-20 min in cats Often the drug of choice for induction for c-sections (rapid metabolism, very little effect on the neonates)

Question 57

Major effects and adverse effects of alfaxalone

Answer 57

Dose dependent CNS depression (sedation to general anesthesia) Minimal cardiovascular depression -HR may increase Hypotension especially when used with inhalant anesthetics Resp depression including apnea especially after rapid injection or high doses Muscle relaxation Excitement may occur during recovery (especially if not good premed or surroundings are noisy)

Question 58

Using alfaxalone

Answer 58

Labelled for induction and short term maintenance in D+C Always give IV, to effect, for induction 5-10 min anesthesia in dogs; 15-30 min in cats Causes induction apnea Patients should be preoxygenated Will cause more resp depression if given too fast IV- give to effect/titrate to effect

Question 59

How is alfaxalone different from propofol

Answer 59

Can store multi dose vials 28 days at room temp after opening Can give IM to cats for sedation

Question 60

Alfaxalone sedation in cats

Answer 60

Labelled for IM sedation in cats Used in combination with butorphanol Will sting on initial injection Gives approx. 40 min of good sedation (variable results) Results improved if also add midazolam Have 100% oxygen on hand in case of hypoxia