Pre-anesthetics: Use alone or in

Combination

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No safe anesthetics, only safe
anesthetists
Drugs for dogs? Drugs for cats?
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Options for Preanesthetic Medication or for
Temporary Restraint and Sedation:
There are many useful options
for an infinite variety of clinical
situations.
What are some of your
favorites?
Balanced, multi-modal, and
individualized
C1Q$-4*.1#'9.$/
Lytic to parasympathetic nervous system
Depress salivary and bronchial secretions
Induces pupillary dilation
Increases heart rate - Dose dependent partial blockade of vagal
tone

Decreases gastric motility and secretions, e.g., ketamine
Prevents severe bradycardia from vagal stimulation, opioids
Avoid in patients with sinus tachycardia or PVCs
Atropine Sulfate
Dose in dog or cat
" SQ: 0.04 mg/kg
" IM: 0.02 mg/kg
" IV: 0.01 mg/kg

Duration of primary action:1/2 - 2 hours
Increase in heart rates
Increase in cardiac work load
Dilation of pupils
Decrease in salivation and gastrointestinal mobility
Glycopyrrolate
Dosage-0.005-0.02 mg/kg IM,IV,SQ
Decreases gastrointestinal mobility
Increase in gastric pH
Half-life = 4 hours
Less likely to cause excess heart rates than atropine
Acepromazine
Phenothiazine neuroleptic tranquilizer

Never use label dose (1.1 mg/kg) UNSAFE!
It is much safer to dilute bottle concentration of 10
mg/ml to 2 mg/ml

Never store near direct
sunlight

Acepromazine
Dosage 0.01 0.1 mg/kg *
Inc sensitivity in breeds with mutation in K9 MDR1
gene?
Total dose less than 2 mg *
Use in patients with seizure history is NOT
recommended

*based on route of administration and
individual patient needs
Expected benefits from the utilization of
minor tranquilizers
(i.e. Diazepam and Midazolam)

Enhances the effects by binding to
benzodiazepine site on GABA receptors
Skeletal Muscle Relaxant
Anticonvulsant
Anxiolytic
Sedative
Hypnotic
Diazepam
ropy|ene g|yco| so|ub|||ty agent
Dose: 0.2 - 0.S mg]kg I.V.

Chen used |n comb|nanon w|th
ketam|ne and an op|o|d for I.V.
|nducnon
Se|dom used as a stand a|one drug
Midazolam
(Versed, Hypnovel)

Water sol benzodiazepine
Use alone - less than 0.5 mg/kg
May be substituted for acepromazine or an
alpha-
2
plus opioid as premedication
Useful for dysphoric patients post operative
Not an analgesic but 0.1 mg/kg reduces
anesthetic requirements
Currently Available Sedative/Hypnotics:
Xylaxine (Rompun)
Yohimbine
Detomidine (Dormosedan)
Medetomidine (Domitor)
Atipamezole
(Antisedan)
Dexmedetomidine
(Dexdomitor)
Xylazine Medetomidine - Dexmedetomidine
(!-
2
: !-
1
affinity)

ky|az|ne: 160:1
Medetom|d|ne 1620:1
Dexmedetom|d|ne 16S0+:1


R CQ2)5#S4*# ./ ) /2#$.T$ )*2-)
U
)1%)941./%

Alpha
2
Agonists:
use for sedation & analgesia
Alpha
2
adrenergic receptor
agonists (*listed in order of clinical release)
C|on|d|ne
ky|az|ne
Detom|d|ne
!"#"$%&'#'("
*%&'+#'("
Dexmedetom|d|ne

VW
(dexmedetom|d|ne hydroch|or|de 0.S mg]mL)
(dexmedetom|d|ne hydroch|or|de 0.1 mg]mL)
Latest available alpha
2
agonist (2013)
Development of Dexdomitor

Dexdomitor is the most
specific and selective new
generation !
2
-adrenoceptor
agonist available to
veterinarians for use in dogs
and cats:
sedation
analgesia
preanesthesia
VX
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Dexdomitor: The Next Generation
UZ
Domitor

(racemic medetomidine)
has been on the market since 1987
and has right- and left-handed
enantiomers
Dexmedetomidine, the right-
handed enantiomer, is the only
active part of the molecule for the
sedative/analgesic and dose-sparing
effects
The left handed enantiomer, is non-
active





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UV
Indications for Clinical Procedures
# Non-invasive, mildly to moderately painful,
procedures and examinations which require
restraint, sedation and analgesia in dogs and
cats
# Deep sedation and analgesia in dogs in
concomitant use with butorphanol for medical
and minor surgical procedures
# Premedication in dogs and cats before
induction and maintenance of general
anaesthesia.
UU
Dosage
Species Indication
Body surface area Body weight*)
Sedative and analgesic to facilitate clinical
examinations or procedures, and minor
surgical or dental procedures
500 mcg/m
2
IM
375 mcg/m
2
IV
20 mcg/kg IM
15 mcg/kg IV
Deep sedation/analgesia in concomitant use
with butorphanol for medical and minor
surgical procedures
300 mcg/m
2
IM
+ 0.1 mg/kg IM
11 mcg/kg IM
+ 0.1 mg/kg IM
Preanesthesia prior to general anaesthesia
375 mcg/m
2
IM
125 mcg/m
2
IM
15 mcg/kg IM
5 mcg/kg IM
Sedative and analgesic to facilitate clinical
examinations or procedures, and minor
surgical or dental procedures
- 40 mcg/kg IM
Premedication before induction and
maintenance of general anaesthesia with
ketamine
-
40 mcg/kg IM
+ 5 mg/kg IM
Preanesthesia prior to general anaesthesia

-
40 mcg/kg IM

U]
* Dog dosages in mcg/kg are for comparison purposes only for an average 15-20 kg animal (1 mcg/kg = 25
mcg/m
2
) Best results are obtained by body surface area dosing.
Dosing by body surface area vs. body
weight
1
0
5
10
15
20
25
30
35
40
0 10 20 30 40 50 60 70 80 90
D
e
x
d
o
m
i
t
o
r

d
o
s
e

(
m
c
g
/
k
g
)
Dog weight (kg)
Dexdomitor dosing for IM sedation/analgesia in dogs
body surf ace area dosing: 500 mcg/m2
body weight dosing
U^
1
see Kilgore et al. 1990
Sample uses of multi-modal
Pre-anesthesia
# Dog: Typical demeanor
" Dexmedetomidine; 1 5 "/kg IM
" Morphine; 0.5 mg/kg IM
" Atropine: # only at same time
# Dog: Fractious / Fearful
" Dexmedetomidine 1.5 2 "/kg IM with opioid
# Cat: Typical demeanor
" Dexmedetomidine; 5 10 "/kg IM
" Morphine; 0.05 mg/kg IM
# Cat: Aggressive / Fearful Bad cats:
" Ketamine; 2 5 mg/kg IM


Antisedan (atipamezole hydrochloride)
Indicated for the reversal of the sedative and other
effects of Dexdomitor and Domitor
Potent alpha
2
antagonist that selectively and
competitively inhibits the alpha
2
adrenoceptor
Longer elimination half-life than for dexmedetomidine
Administered IM
in dogs, same dose volume as Dexdomitor 0,5 mg/ml but 1/5 volume
as Dexdomitor 0,1
in cats, half the dose volume as Dexdomitor 0,5 mg/ml but 1/10
volume as Dexdomitor 0,1
Reversal of Dexdomitor within 5 to 15 minutes
Side effects are rare:
vomiting, hypersalivation, diarrhea, muscle tremors, and excitation
U_
Opiate or Opioid
Opiate: Any drug derived
from opium, e.g. morphine
Opioid: Any synthetic
narcotic with opiate-like
activity, but is not derived
from opium, e.g. fentanyl
Morphine
" First opioid used in animal pain
management
" Opioid, is the Gold Standard, to
which all other opioids are compared
" Dosage:
dog: 0.2 0.5 mg/kg
cat: 0.02 0.1 mg/kg
" Potent analgesic properties: dosage
depends on route of administration,
pain level and responses
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Morphine
Demerol
Oxymorphone
Hydromorphone
Fentanyl
Sufentanil
Remifentanil
Butorphanol
Buprenorphine
Tramadol
Naloxone (antagonist)
(#1%)1+*
1960 - Ianssen
harmaceunca|s
Strong mu-op|o|d agon|st
7S - 100 k potency of
morph|ne
W|de|y used |n humans and
sma|| an|ma|s
Dose:
dog: 2 - 10 g]kg IM, IV
cat: 1 - S g]kg IM, IV
Cr may be used as a patch
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Dose]koute

Duranon

Ind|canon
s

Comments
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Mu Opioid Agonists Continued
# Hydromorphone:* Dosage:
" Dogs: 0.1-0.2 mg/kg IM,IV,SQ
" Cats: 0.05- 0.1 mg/kg IM,IV,SQ
# Oxymorphone:* Dosage:
" Dogs: 0.05-0.1 mg/kg IM,IV,SQ
" Cats: 0.025-0.05 mg/kg IM,IV,SQ
*Provides moderate to profound analgesia lasting 2-4
hours (Hydromorphone) and 3-4 hours (Oxymorphone)


Transdermal Opioid Pre-anesthesia
The fentanyl patch$effective but not officially approved for veterinary
usage in many countries. Available in four sizes releasing fentanyl at
25, 50, 75, and 100 micrograms/hour. Apply 8 to 12 hours prior to
anesthesia.
Dosages
# Cats: 25-50 mcg/hour patch
# Dogs: 3-10 kg25/hour patch
" 10-20 kg-50/hour patch
" 20-30 kg-75/hour patch
" 30 kg100/hour patch
Transdermal Fentanyl Guidelines
Must be in contact with skin for
effective usage in dogs or cats
Absorption is slow: allow 8-12 hours for
desired analgesia
Duration is up to 72 hours
Caution: Keep away from children and
avoid accidental human exposure
Opioids by Constant Rate Infusion
Fentanyl in dogs and cats (IV administration)
" Dogs: loading dose (0.002 mg/kg) followed by 0.001-0.006 mg/kg/
hour
" Cats: loading dose (0.001-0.002 mg/kg) followed by 0.001-0.004 mg/
kg/hour

Sufentanil in both dogs and cats (IV administration)
" Loading dose (0.002-0.005 mg/kg) followed by 0.0001-0.0002 mg/kg/
hour
* Adjust dosages for each patient needs and responses
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* Do NC1 use 1ramado|]
Acetam|nophen
comb|nanon |n cats
P)'1.19
Tramadol Activity
40 mu-op|o|d
agon|st
40
Noradrena||ne
uptake
|nh|b|non
20 Sn1
uptake
|nh|b|non
Tramadol Dosage and Duration
Dogs
# 0.1-0.2 mg/kg IM or IV
# 1-10 mg/kg orally based on
level of pain
# Duration, 2-4 hours

Cats
# 0.05-0.1 mg/kg IM or IV
# 1-2 mg/kg orally based on
level of pain
# Duration , 2-4 hours

Opioid Agonist Side Effects
Excessive CNS depression
Respiratory depression
Cardio vascular depression
CNS excitement / delirium
Vocalization
Treat as symptoms indicate
Excessive dose

May need oxygen

Reduced rate and output

Agent specific ?

Individual response, may need
adjunct tranquillizer

May reverse with antagonist if
adverse effects persist


Opioid Antagonists
Used to treat opioid side effects/adverse
responses
Naloxone: can antagonize the effects of opioid
agonists including sedation, respiratory depression
or excitement
Dosage: 1-25 micrograms/kg IV slowly and to
desired effect. Start with low doses.
Duration of effects: up to one hour in dogs and up
to four hours in cats
Warning: Acute pain symptoms may return
following reversal of the opioid agonist
Opioid Agonists/antagonists
! Usage alone or in combination with tranquilizers or
sedatives is increasing in clinical practice
Buprenorphine Butorphanol
Currently Available Agonist-Antagonists

* Marketed in Europe as Butomidor ** Marketed in Europe as Bupaq
Pentazocine

Naloxone (antagonist)

Nalbuphine

Buprenorphine **
Butorphanol *
Buprenorphine HCl
Approved in Europe as Bupaq vet 0.3mg/ml
solution for injection
Indications:
# Dogs: Post-operative analgesia
" Potentiation of the sedation effects of centrally
acting agents
# Cats: Post operative analgesia
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Buprenorphine Duration
As sole medication:
" Mild sedation -15 minutes post injection
" Analgesia - 30 minutes post injection
" Peak effect 1-1.5 hours
" Expected duration- up to 6-8 hours
In combination with other analgesics, sedatives or
anesthetics.. adjust dosages due to synergistic
effects on duration and patient responses
Buprenorphine Contraindications
Hypersensitivity to active substance
or any excipients
By intrathecal or peridural route of
injection
Pre-operatively for Caesarian
section
Butorphanol Tartrate ,10mg/ml*
Marketed in Europe as Butomidor
# Indications: Horse
" As a short term analgesic
" As a sedative and pre-anesthetic
(combine with an alpha
2
agonist)
# Indications: Dogs and Cats
" As an analgesic
" As a sedative
" As a pre-anesthetic and part of the
anesthetic protocol
Butorphanol Dosages:
Route of Administration in Dogs
# Sole medication for post operative pain
" 0.1-0.4 mg/kg (0.01-0.04 ml/kg) slowly IV, IM, or SQ
# As a sedative/analgesic:
" Butorphanol, 0.1 mg/kg IV,IM plus
" Medetomidine, 0.01 mg/kg IV,IM
# As a preanesthetic:
" Butorphanol, 0.1 mg/kg IM plus
" Medetomidine, 0.025mg/kg IM
(example-15 minutes later may induce with ketamine also known as Ketamidor or Ketaset )
Butorphanol Dosages:
Route of Administration in Cats
# As an analgesic:
" 15 minutes prior to anesthetic recovery:
" 0.4mg/kg SQ or 0.1 mg/kg IV
# As a sedative/analgesic:
" Butorphanol, 0.4 mg/kg SQ plus
" Medetomidine , 0.05 mg/kg SQ
# As a pre-anesthetic:
" Butorphanol, 0.1 mg/kg IV plus
" Medetomidine, 0.04 mg/kg IV which may be followed with
ketamine, average dose of 1.5 mg/kg IV. Dose to desired effect!
Duration of Analgesia
# Mild sedation - 5 minutes post injection
# Analgesia - 5 minutes post injection
# Peak effect 20-30 minutes
# Expected duration - up to 1-4 hours
depending on dosages and sole vs
combined drug responses.
Opioid /Alpha
2
Agonists
Advantages
Reversible
Many combinations in use
Provide profound sedation and analgesia
Significantly reduce anesthetic dose requirements


Opioid Agonists/Alpha
2
Agonists
Side Effects
Bradycardia
Reduced perfusion
Respiratory depression
Reduced oxygen saturation

Opioid Agonist-antagonist/Alpha
2
agonists
# Provides desirable sedation and analgesia
# Opioid duration prolonged by alpha
2
agonist
# Alpha
2
cardiovascular side effects reduced by the opioid
# Reduced dosages of each drug
Pre-anesthesia in the Difficult / Mean
Patient
WARNING
Avoid in patients with respiratory
compromise, HCM!!!, seizure history,
increased IOP and ICP



Anger Management in Aggressive
Patients
Ketamine or Telazol Combinations With Alpha
2
Agonists And
Or Opioids

Advantages
# May be administered SQ or IM
# Safety factors to patients as well as
personnel
# Physiologic stability
# Recovery within 2 hours, but
occasionally delayed

Balanced Analgesia
Multi-Modal Analgesia
Similar to "balanced anesthesia
Combination of complimentary methods or drug classes
Maximize effectiveness and minimize side effects of each
drug = balanced
Multimodal
Balanced Analgesia
Acepromazine & Opioid
Ace at 0.025 mg/lb (0.05 mg/kg), max 1.0 mg, IM, or IV
Hydromorphone at 0.05 mg/lb (0.1 mg/kg) IM, or IV
# Substantial and reliable
# Not recommended for older or
compromised patients
# Prolonged effect (+++)
# Return to Cognitive recovery
often requires 4-6 hrs. +
# Optional anticholinergics
# Alternative opioids$
Diazepam or Midazolam & Opioid
Combinations

Mild and gentle effect
Inadequate for vigorous patient
Analgesic duration approximately 30
minutes
Cognitive recovery in 1-2 hours?
Reduced doses of diazepam or
midazolam are often adequate
Hydromorphone 0.05 mg/lb (0.1 mg/kg) IM, or IV. Followed by:
Diazepam or Midazolam 0.1 mg/lb (0.2 mg/kg) IM or IV (only IV for Diazepam)
Example
Some More kecent re-anesthenc rotoco|s In
Sma|| An|ma|s
ASA Physical Status 1 or 2

# Dexmedetomidine: 2.5 "g/kg; (3.0 for younger, smaller breeds)
# Butorphanol: 0.2 mg/kg
# Propofol :0.5 1 mg/kg
# Sevoflurane following ET intubation
Some More Recent Pre-anesthetic
Protocols In Small Animals (continued)
ASA Physical Status 3

# Same protocol or,
" Midazolam :0.3 mg/kg
" Butorphanol: 0.2 mg/kg
" Propofol : 0.5 1 mg/kg
Controversies with Perioperative Drugs
# Tranquilizer Acepromazine
" Evidence of increased risk with
seizure history no
" Breeds questionable?

# Anticholinergic Atropine
" Pre-emptive - indications?
" Indiscriminant use no
" With alpha
2
agonists - questionable?


Controversies in Use of Pre-anesthetics;
When to use atropine

Originally used to prevent bradycardia and excessive salivation during morphine/
diethyl ether anesthesia
Currently used to prevent bradycardia

Is it needed with currently used pre-anesthetics?
Is it needed with new inhalant anesthetics?


Conclusion !$Should be based on individual patient needs

Use of Atropine with Alpha
2
Agonists

# Helps maintain higher heart rates
# Prolongs hypertension
# Increases myocardial oxygen demands
# Increase in cardiac arrhythmias following IV administration
during alpha
2
sedation
# Not routinely recommended

Additional Controversies

# Analgesics are not needed during general anesthesia
# Most anesthetics have inadequate analgesic properties
when used alone but$ Anesthetic/analgesic combinations
provide desirable perioperative pain management
Controversies Continuing

# Alpha
2
Agonists are anesthetics at high
doses?
" High doses prolong sedation analgesia,
side effects and recovery times
# Ketamine has excellent anesthetic and
analgesic properties when used alone? (this
is not proven)
# Ketamine provides somatic analgesia but
inadequate visceral analgesia?
" Ketamine in combination with pre-
anesthetics are very useful clinical
protocols
Patient Preparation
# Equipment check list
* Oxygen Supply
* CO
2
absorbent
* ET tube and mask
* Breathing system
* Inhalant anesthetic
* Scavenging system
* Electronic monitoring
# IV catheter and fluids
G48 P# C'# I#)3+ %4 F13&$# )13
A).1%).1 C1#/%-#/.)

re oxygenanon
Inducnon
Intubanon
Maintaining Anesthesia
# Many options including:
" Multiple IV injections or constant
rate infusions of injectable
anesthetics
" Inhalant anesthetics ( isoflurane or
sevoflurane)
" Concurrent usage of local or
regional nerve blocks
,-)1O
H4& ?'J
@#%
Special Recognition
# We appreciate the unrestricted
educational grant from Richter Pharma,
Wels, Austria and their impute and
encouragement