Pain Management in the

Surgical Patient
Peter Vogel, VMD, DACVS
Pain Pathways

u Specialized neurons that travel through the spinal

cord
u Free nerve endings in skin, connective tissue,
muscle and bone
u Cell bodies in the dorsal root ganglia
Pain Pathways

u Afferent system consisting of 3 neurons

u Cell body that bifurcates with one end in the
peripheral tissue and one in the dorsal horn
u Second order neurons ascend in the contralateral
spinothalamic tract
u Third order neurons in the contralateral thalamus
project to the somatosensory cortex
Acute Pain

u Acute pain is usually nociceptive pain

u Tissue damage leads to activation of small nerve endings
and inflammatory cells
u Inflammatory mediators cause pain via nociceptive
stimulation and increased excitability of nerve endings
u NOTE: Complex system, not just neurons involved**
u Pain management strategies should target as
many aspects of the nociceptive response as
possible
u Variety of pain receptors and mediators can be
manipulated and controlled via pharmacologic
intervention.
Pre-operative Medications

u All surgical patients should have pre-operative

pain medication
u General anesthesia blocks the brain from
feeling pain, but does not prevent activation of
the local and spinal pain pathways (ramp up)
u Itis better to prevent stimulation of the
nociceptive pathways than try and treat them
post-operatively.
Pre-operative Medications

u Nociceptive pathways are activated both by inflammation

and direct neuron stimulation
u Narcotics will help decrease neuronal stimulation
u NSAIDS will help minimize inflammatory stimulation

u Unless contra-indicated, both should be given

Butorphanol

u Mixed agonist-antagonist
u More sedatory than analgesic
u Fairly rapid onset
u Analgesia lasts 1-3 hours
u Bonds more tightly than pure agonists
u Appropriate for mild-moderate pain only
Buprenorphine

u Partial Mu agonist
u SLOW ONSET (20 minutes minimum)
u Lasts 4-8 hours at common dosages
u Used for mild-moderate pain
u Well tolerated in cats
u Buprenorphine displaces morphine, methadone, and other full
opioid agonists from receptors. It also can block the effects of
other opioids.
u Extreme receptor affinity (not reversed by naloxone) but low
intrinsic activity
u The main reason for use of butorphanol and
buprenorphine in the past was that they were not
controlled substances
u There are better narcotics for use in operative patients
Morphine

u Prototypical opioid
u Onset of action 15-30 minutes
u Hepatic metabolism and renal excretion (use with caution
in patients with renal disease)
u Can be used in cats!!
u “Morphine Mania” is due to inappropriately high doses
in cats
u Causes mydriasis rather than miosis in cats
Morphine

u Cardiovascular depression
u Dose dependent respiratory depression
u Low lipid solubility (slow onset IV), useful for epidural
injection
u Can be given intra-articularly (0.1 mgs/kg diluted in
saline)
u Oral forms have low bio-availability
u Histamine release
Hydromorphone/Oxymorphone

u 5-10X more potent than morphine

u Does not cause histamine release
u 15-20 minute onset of action IV, lasts 2-6 hours
u Much slower onset when given IM or SQ
u Hyperthermia in cats (not responsive to naloxone)
u Must monitor temperature
Fentanyl

u 100X more potent than morphine

u High lipid solubility = rapid onset of action
u Rapidly redistributed = short duration of action
u Can be given IV, IM, epidurally, transmucosally,
and transdermally
u Usually given as an IV bolus followed by a CRI
Methadone

u Methadone is a mu-receptor (OP3; MOR) agonist that also

is a non-competitive inhibitor of NMDA (n-methyl-d-
aspartate) receptors. Methadone can also reduce re-
uptake of norepinephrine and serotonin, which may
contribute to its analgesic effects. Due to these other
actions, methadone potentially may be more efficacious
than other mu- agonists (e.g., morphine) particularly for
neuropathic or chronic pain. Methadone is more lipid-
soluble than morphine and approximately 1-1.5X as
potent. It does not cause significant histamine release
when administered intravenously.
Methadone

u Usually given as an IV CRI

u Can be dosed IV, IM, and SC
NSAIDS

u Unless contra-indicated, all surgical patients should

receive injectable NSAIDs pre-operatively
u Yes, you can give NSAIDs to cats
u Meloxicam (0.05-0.1 mgs/kg IV/SQ)
u Robenicoxib (Onsior) (2 mgs/kg IV/SQ)
u Reduces inflammation and release of inflammatory
mediators
Post-operative Pain Management

u If your pre-operative protocol is effective, post-

operative pain management will be much easier
u Far easier to prevent activation of nociceptive
pathways than to suppress them later
Pain Assessment

u CSU pain score chart (see handout)

u Cats and dogs show pain differently
u If in doubt, assume the patient is painful
u Best indication is behavior
Pain vs Dysphoria

u Can be difficult to differentiate pain vs. dysphoria

secondary to general anesthesia
u Micro-dose Dexmedetomidine test:
u 1-2 mcg/kg IV
u If dysphoric, patient will respond
u If painful, minimal response seen
Opioids

u All patients should receive post-operative opioid analgesia

u Dosages and effects/actions similar to pre-operative

u Vomiting post-operatively from opioids is uncommon

Butorphanol

u Useful for mild-moderate pain

u Slow onset, short duration of action for analgesia, longer
for sedation
u Often combined with dexmedetomidine or acepromazine
u Caution in compromised patients
u Probably should not be used for any patient where
significant pain is anticipated
u Pure agonist can be administered if needed
Buprenorphine

u Very slow onset of action

u Threshold effect (giving more does not increase pain
relief)
u Higher doses do, however, last longer
u 50 mcg/kg will last 24 hours
u Cannot give any other opioid if buprenorphine is not
effective due to high binding affinity
u Can be used to reverse other opioid without removing all
pain control
Hydromorphone/Oxymorphone

u Commonly given at 0.1 mg/kg q 4-6 hrs as needed

u Dose can be increased if necessary
u Given IV, IM, or SQ
Methadone

u Effective as CRI or as intermittent dosing (q4-6

hrs)

u Slightly more effective than morphine

Methadone

u Dogs: 0.1-0.2 mgs/kg IV followed by CRI @ 0.12

mgs/kg/hr OR 0.1-1.0 mg/kg q4-8 hrs IV. IM, SQ
u Cats: 0.1-0.2 mgs/kg IV followed by CRI @ 0.12
mgs/kg/hr OR 0.05-0.5 mg/kg q 4-6 hrs IV, IM, SQ

u Oral form poorly absorbed

Fentanyl

u Usually used as a CRI (2-8 mcg/kg/hr)

u Requires infusion pump
u Bolus can be given and CRI rate increased if pain control
inadequate
u CRI should be tapered over 12-24 hours as other pain
control medications are taking effect.
u Very short duration
Medications TGH

u What options do we have?

u How effective are they?
Oxycodone

u Poor bioavailability
u High potential for abuse by owner
Codeine

u Poor bioavailablity
Acetaminophen/Hydrocodone

u Acetaminophen is ineffective but well tolerated

in dogs as long as the dosage is not too high
u Acetaminophen is highly toxic to cats

u 0.22-0.5 mg/kg Hydrocodone

u DO NOT EXCEED 15 MG/KG ACETAMINOPHEN
u 20 kgs or larger for tablets
Fentanyl Patch

u 12-24 hours for onset (should be used with another agonist

initially)
u Can be removed if side effects are significant
u Potential for abuse by owner
u Potential for accidental exposure to owner
u Potential for accidental ingestion by pet
u Typically lasts 72-96 hours
Fentanyl Patch

u Available from 12-100 mcg/hr, sized by weight of patient

u DO NOT CUT PATCH
u Can use more than one patch if patient over 40 kgs
u Variable absorption
u Dependent on placement, adherence, obesity, temperature
Transdermal Fentanyl (Recuvrya)

u Super-concentrated form of fentanyl for transdermal

absorption
u Rapid onset of action (2 hours or less)
u Lasts up to 5 days
Transdermal Fentanyl

u Like all “depo” drugs, it cannot be removed if side effects occur

u Dysphoria
u Urine retention
u Excessive sedation

u Requires continual reversal to overcome side effects for many days

u High dose buprenorphine daily
u Naloxone q 4-6 hours
Tramadol

u Unlike in people and cats, dogs do not

metabolize Tramadol to the active form (M1) to
any significant degree
u Minimal narcotic effect in dogs
TRAMADOL: WHAT DO WE REALLY KNOW?
Sandra Z Perkowski, VMD, PhD, DACVA
University of Pennsylvania School of
Veterinary Medicine, Philadelphia, PA
Tramadol is a centrally acting analgesic with low affinity for the mu opioid
receptor and with an analgesic action that may be primarily related to inhibition
of norepinephrine and serotonin reuptake
The M1 metabolite is the only one shown to be clinically active but has recently
been shown to be a relatively minor metabolite in dogs, with plasma levels being
lower than those associated with analgesic effects
Pharmacokinetic studies have raised questions regarding appropriate dose and
dosing intervals for tramadol and more studies proving efficacy are needed.
Pharmacokinetics in Dogs

u After oral administration in dogs, tramadol is rapidly and extensively metabolized

by cytochrome P450 enzymes (CYP) to several metabolites, only one of which,
Odesmethyltramadol (M1), has been shown to be clinically active. O-
desmethyltramadol has a much higher affinity (200X) for the mu opioid
receptor than the parent compound although the affinity is still only 10% that
of morphine. It was previously suggested that rapid metabolism to the more
potent M1 metabolite was responsible for the majority of tramadol’s analgesic
effect.
u Giorgi et al (2009) found that tramadol was rapidly absorbed after oral
administration of an immediate release capsule (4 mg/kg), but then rapidly
metabolized to two other main metabolites the M5 (N,Odesmethyltramadol)
and M2 (N-desmethyltramadol) metabolite, rather than the M1 metabolite.
KuKanich and Papich (2011) similarly found M1 to be a minor metabolite after a
dose of 10mg/kg tramadol in Greyhounds. The half-lives of both tramadol and all
three metabolites were relatively short (tramadol: 1.1hr vs M1: 1.4 hr).
Tramadol Dosage

Simulated dosing of tramadol suggested that 5 mg/kg q 6 hours or 2.5 mg/kg q 4

hours was required for adequate analgesic levels. This is in contrast to the 2 – 4
mg/kg bid/tid generally recommended.
In human patients, oral tramadol has been shown to be effective in some
patients with moderate cancer pain, although efficacy is dependent upon the
source of pain, with 83% efficacy in patients with bone pain, but only 33%
efficacy in patients with neuropathic pain.
Another study comparing the efficacy of celecoxib vs. tramadol in treatment
of patients with chronic low-back pain found celecoxib to be more effective
than tramadol, with fewer adverse events.
Tramadol

u Action appears to be predominantly on

neurotransmitters (serotonin and norepinephrine)
u Action similar to fluoxetine
u Serotonin syndrome is possible (do not use with
other SSRIs)
u Blood levels drop dramatically after 14 days of
administration
u We are all likely using this drug incorrectly in dogs
Tramadol

u The major reason for the use of tramadol was

safety and it was not a controlled substance.
u Use for more than 14 days is likely contra-
indicated
u Does not provide analgesia like opioids do
u Does seem somewhat effective. Fluoxetine or
Trazadone may be just as effective and are not
controlled.
NSAIDs

u NSAIDS have been shown to be as effective as

opioids in numerous controlled clinical trials in
humans and our pets
u Particularly more effective in dogs than Tramadol
u Not surprising given Tramadol’s lack of mu agonist
activity in the dog
NSAIDs: Dogs

u A variety of injectable and oral NSAIDs available

u Cox2 inhibitors can be mixed and matched
u Carprofen
u Meloxicam
u Deracoxib
u Firocoxib
u Robenicoxib
u Grapiprant: EP4 inhibitor
NSAIDs: dogs

u Carprofen is the least selective Cox 2 inhibitor

u Can cause reversible platelet inhibition
u Prefer to avoid use 12-24 hours pre-operatively
Other NSAIDs

u No justification for use of older NSAIDs

u Off label use
u More side effects
u Aspirin should not be used with surgery
NSAID: cats

u Both Meloxicam and Robenicoxib can be used

safely in cats
u Meloxicam licensed for use in cats in Europe
u Off label use in US (black box warning!!)
u Robenicoxib approved for long term use in cats
in other countries
u Even aspirin can be used safely in cats, given at the correct dose (low dose: 81mgs q 72 hours), but you didn’t
hear that from me
NSAIDs: Cats

u Feline renal function does not depend on the

cyclooxygenase pathways
u Dosage of meloxicam in cats is significantly lower than in
dogs (0.03-0.05 mgs/kg q daily)
u Previous reports leading to black box label were based
on dramatically higher dosages
u Use Robenicoxib if you wish to avoid off-label use of
Meloxicam. However, use beyond 3 days is off-label in US
(but not Europe/Australia)
NSAIDs

u DONOT GIVE NSAIDS TO ANY PATIENT

WHO IS ON OR WHO HAS RECEIVED
STEROIDS WITHIN 72 HOURS
Other Modalities

u Gabapentin
u Indicated for neurogenic pain (not nociceptive pain)
u Despite the frequent recommendation for using gabapentin to manage chronic pain in
dogs, there is little data available evaluating its efficacy. A double blinded study did not
find a short-term benefit of gabapentin on postsurgical pain.

u Trazadone
u Large safety margin
u SSRI
u Probably very similar to Tramadol in dogs
u Seems as effective as Tramadol IMHO
u Not a controlled drug
Other Modalities

u Neuraxial Anesthesia
u Epidural and intrathecal pain control
u Opioids or lidocaine
u Preservative free
u Can be quite effective, learning curve required
u Most useful for pelvic limb procedures
u Possibility of respiratory depression, bradycardia, and
sympathetic blockade
Other Modalities

u Local blocks: local anesthesia given before or during

surgery
u Particularly effective for thoracotomy and amputation
u Can be given IA
u Topical, local infiltration, nerve blocks, distal limb
blocks, brachial plexus blocks, intercostal nerve block,
MUMR block
u Bupivicaine lasts longer than lidocaine
u Nocita (bupivacaine liposome)
Nocita

u Bupivicaine liposome suspension

u 72 hours of post-operative analgesia
u Extended release formula
u Limited lifespan once vial is opened
u Infiltration of each tissue layer at closure
u Expense
u Only approved use is TPLO
Questions??
Induction Adjuvants

u • Dexmedetomidine (0.5-1 gg/kg IV) or

u • Medetomidine (1-2 gg/kg IV) plus
u • Ketamine (0.5-1 mg/kg IV) plus
u • Fentanyl (2-10 mg/kg IV PRN: for short term pain relief)
CRI
u Hydromorphone (0.025-0.1 mg/kg/hr IV) or Fentanyl (1-10 mcg/kg/hr loading dose),
then10-30 mcg/kg/hr intraoperatively and 2-20 mcg/kg/hr IV postoperatively
u Dexmedetomidine (2.5-5 mcg/kg IV loading dose),then 0.5-1 mcg/kg/hr
u Ketamine (0.5 mg/kg IV loading dose), then 10 mcg/kg/min IV CRI intraoperatively and
2 mcg/kg/min IV CRI postoperatively
u FLK
u Fentanyl (1-5 mcg/kg/hr IV) plus
u Lidocaine (25-50 mcg/kg/min IV) plus
u Ketamine (2-5 mcg/kg/min IV)
u MLK (not recommended for cats)
u Morphine (3.3 mcg/kg/min IV) plus
u Lidocaine (50 mcg/kg/min IV) plus
u Ketamine (10 µg/kg/min IV)
u HYDROMORPHONE- Dogs: 0.1-0.4mg/kg IM/SQ/IV Cats: 0.05-0.2mg/kg
IM/SQ/IV **vomiting is more common after IM administration. Onset 10-20
minutes, duration 4-8 hours.
u OXYMORPHONE- Dogs: 0.05-.2mg/kg IM/SQ/IV Cats: 0.025-0.1 mg/kg
IM/SQ/IV. Rapid onset, duration 4-6 hours.
u MORPHINE- Dogs: 0.5-1mg/kg IM/SQ/IV Cats: 0.25-.05mg/kg IM/SQ/IV. Rapid
onset, duration 4- 6 hours. Potential to cause transient hypotension, often
causes vomiting with IM or SQ use, and may cause histamine release with IV
use.
u FENTANYL- Loading dose of 2-5 ug/kg followed by 2-45 ug/kg/hr IV CRI. Note-
if animal is premedicated with another pure mu agonist, it may not be
necessary to give a loading dose of the fentanyl.
u METHADONE- Dogs: 0.5 to 1.0 mg/kg IM/SQ/IV Cats: 0.25 to 0.5 mg/kg IM/SQ/
slow IV. Rapid onset, duration 4-6 hours. Least likely to cause vomiting.
u BUPRENORPHINE- Dogs: 0.005-0.03 mg/kg IM/SQ/IV Cats: 0.005-0.01mg/kg
IM/SQ/IV, 0.005- 0.03 buccal. Onset 30-60 minutes, duration 4-12 hours
depending on the dose.
u BUTORPHANOL- 0.1-.04mg/kg IM/SQ/IV. Rapid onset, duration 1-3 hours. Not
recommended for somatic (orthopedic/joint/muscle) pain.
u CODEINE: 0.5-2mg/kg PO BID-QID.
u TYLENOL/HYDROCODONE: 0.22-0.5 mgs/kg Hydrocodone.
Do not exceed 15/mg/kg Acetaminophen
u 20 kg dogs or larger for tablets
u Liquid for smaller patients
Hydrocodone/Acetaminophen Oral Tablets: 5 mg/300 mg, 5
mg/325 mg, 7.5 mg/300 mg, 7.5 mg/325 mg, 10 mg/300 mg, &
10 mg/325 mg.

An oral solution containing hydrocodone 2.5 mg/5 mL in

combination with acetaminophen 167 mg/5 mL (0.5 mg/mL
hydrocodone and 33.3 mg/mL of acetaminophen) is also readily
available. Commonly used trade names for these products
include: Vicodin®, Norco®, and Lortabs®. They are all Rx; C-
II in the USA.