7. Analgesia

1Copyright © 2011, 2003, 2000, 1994 by Mosby, Inc., an affiliate of Elsevier Inc.

Controlling Pain

Analgesia

Chapter 7


Physiology of Pain

Nociception: detection by the nervous system for the potential for, or actual tissue injury Protects animal from painful or noxious stimuli

Physiologic pain Ouch pain Little or no tissue injury

Pathologic pain Follows tissue injury Acute or chronic


Pathologic Pain

Classification based on mechanism Inflammatory, neuropathic, cancer, idiopathic

Classification based on origin Visceral or somatic: superficial or deep

Classification based on severity of pain None, mild, moderate, severe


Nociception: The Pain Pathway

Step 1: transduction Transformation of stimuli into sensory electrical

signals (action potentials) Step 2: transmission

Sensory impulses conducted to spinal cord Step 3: modulation

Impulses are either amplified or suppressed Step 4: perception

Impulses are transmitted to the brain where they are processed and recognized


Nociception: The Pain Pathway (Cont’d)

Each step has different receptors Drugs can be selected that will target specific

receptors and block a specific step Multimodal therapy: targeting two or more of the

receptors


Consequences of Untreated Pain

Catabolism and wasting Immune system suppression Inflammation and delayed wound healing Anesthetic risk and increased anesthesia

doses Patient suffering


Primary Hyperalgesia

Peripheral hypersensitivity Results from tissue damage and constant

stimulation of nerves Area close to the site of tissue injury

becomes painful when stimulated with non-noxious stimuli


Secondary Hyperalgesia

Central nervous system hypersensitivity or windup

Area of hypersensitivity is further away from the site of tissue injury

Results from constant stimulation of spinal cord neurons

Neurons become hyperexcitable and sensitive


Physiologic Changes Caused by Pain

Neuroendocrine changes: can result in a catabolic state and wasting ACTH release Elevated cortisol, norepinephrine, and epinephrine Decreased insulin

Sympathetic stimulation: can result in cardiac arrhythmias Vasoconstriction Increased myocardial work Increased myocardial oxygen consumption


Signs of Pain in Animals

Pain elicits a stress response Stress-related pain results in “fight-or-flight”

physiological response Avoid anthropomorphosis


Preemptive Analgesia

Administration of pain medication before the pain occurs

Commonly involves adding analgesic to premedication prior to anesthesia

Reduces overall requirement for analgesia and duration of administration

Prevents windup


Behavioral Responses to Pain

Vary depending on species, age, breed, and temperament Young patients less tolerant Cattle very stoic Large dog breeds more stoic than small toy

breeds Cats hide; dogs seek owner comfort; herd animals

separate themselves Vary depending on nature, duration, and

severity of pain Vary on the presence or absence of humans


Physical Evidence of Pain

Changes in gait and level of activity Evidence of arthritic pain

Reluctance to lie down or constantly shifting position Evidence of thoracic or abdominal pain


Physical Evidence of Pain (Cont’d)

Vocalization Whine, growl, whimper, groan, snarl, bite, hiss,

grunt, or purr Emergence delirium

• Immediate postoperative vocalization Changes in facial expressions, appearance,

and attitude


Pain Assessment Tools

Verbal rating scales Simple descriptive scales Numeric rating scales Visual analogue scales Comprehensive scales


Pain Assessment Tools: Verbal Rating Scales and Simple Descriptive Scales


Pain Assessment Tools: Numeric Rating Scales


Pain Assessment Tools: Visual Analogue Scales


Pain Assessment Tools: Comprehensive Scales


Assessing Response to Therapy

Acute surgical pain vs. chronic pain Hourly vs. monthly With effective analgesia, pain-associated

behaviors will recede Appetite, grooming, body position or posture,

interaction with people With effective analgesia, pain assessment

scores will decrease


Effective Postoperative Analgesia


Perioperative Pain Management

Preemptive analgesia Begins in preoperative period with premedication May be administered as part of anesthetic

premedication Transdermal fentanyl patch NSAIDs primarily in large animals

Multimodal therapy The use of more than one drug to control pain Cover multiple receptors and mechanisms of

action Reduce dose of individual drugs and anesthetic

agent


Pharmacologic Analgesic Therapy

Analgesia is needed at every stage of hospitalization and treatment Preanesthetic period Surgical period Immediately postoperative period Remainder of hospital stay At home


Pharmacologic Analgesic Therapy (Cont’d)

Choice of drug depends on: Severity and type of pain Patient’s general condition Route of delivery


Using Opioids as Analgesics

Vary in potency, duration, and adverse effects Injectable premedication

Often in combination with a tranquilizer (acepromazine or dexmedetomidine)

Diminish windup Duration of action is 2-4 hours, so not good for

postoperative pain Induce state of potent sedation

Neuroleptanalgesia Provides analgesia throughout surgery and for

some time postoperatively


Using Opioids as Analgesics (Cont’d)

Postoperative analgesia Alone or in combination with other drugs

Sedative and antianxiety drug Excitement in awake cats and horses

Gastrointestinal effects Initial increased gastrointestinal activity: nausea,

vomiting, defecation Followed by a slow down in gastrointestinal

activity: ileus, colic, constipation Metabolized in the liver


Opioid Agents: Morphine

Schedule II drug (United States) and narcotic (Canada)

Used for moderate to severe visceral or somatic pain Preanesthetic and analgesic Pure agonist with affinity for mu and kappa opioid

receptors May cause excitement or dysphoria in cats and

horses May cause restlessness in dogs and horses


Opioid Agents: Morphine (Cont’d)

Administered IV, IM, SC, intraarticular, epidural, or spinal injection

Adverse side effects Initial gastrointestinal stimulation in dogs and cats Ileus and colic development in horses Excitement, miosis (dogs), mydriasis (cats),

hypothermia, hyperthermia (cats) Bradycardia, panting, increased intraocular

pressure, urinary retention Physical addiction (humans)


Opioid Agents: Oxymorphone

Pure opioid agonist Greater analgesic potency and sedative effect

than morphine Fewer side effects and longer duration of

effect than morphine Fewer tendencies to induce vomiting Administered IV, IM, SC, or epidural

May use concurrently with a tranquilizer Expensive Schedule II drug (United States)

and narcotic (Canada)


Opioid Agents: Hydromorphone

Opioid agonist Less potency but similar duration of effect

compared with oxymorphone Administered IV, IM, SC to dogs and cats

Used as a premedication alone or with a tranquilizer

Less expensive than oxymorphone Schedule II drug (United States) and narcotic

(Canada)


Opioid Agents: Methadone

Synthetic opioid Characteristics similar to oxymorphone and

hydromorphone Least likely to cause vomiting in cats and

dogs Antagonist at the NMDA receptor


Opioid Agents: Fentanyl

One of the most potent analgesics known Rapid onset (2 minutes) and short duration of

effect (20-30 minutes) when administered IV Administered by continuous IV drip,

transdermal patch, IM, SC, or epidural injection Used in combination with midazolam or diazepam

drawn into separate syringes Schedule II drug (United States) and narcotic

(Canada)


Opioid Agents: Meperidine/Pethidine

Pure opioid agonist with less potent analgesic properties and shorter duration of action

Administered by SC injection Wide margin of safety Used mostly as a preanesthetic in combination

with atropine or acepromazine When used with a tranquilizer, it provides effective

neuroleptanalgesia in puppies Used with injectable NSAIDs to provide analgesia

before NSAIDs take effect Schedule II drug (United States) and narcotic

(Canada)


Opioid Agents: Butorphanol

Synthetic opioid with agonist and antagonist properties Stimulates kappa receptors and blocks mu

receptors Not as effective an analgesic as a pure agonist Produces less sedation, dysphoria, and respiratory

depression Can be used to reverse the effects of morphine

and fentanyl


Opioid Agents: Butorphanol (Cont’d)

Used as a preanesthetic, sedative, and postoperative visceral analgesic

Administered IV, IM, SC, or orally (as tablets for long-term analgesia) Constant rate infusion IV can prevent redosing

Schedule IV drug (United States) and controlled drug (Canada)


Opioid Agents: Buprenorphine

A partial mu agonist that produces some analgesia for mild to moderate pain Used to provide postoperative analgesia to dogs and cats Can be used to reverse the effects of morphine and fentanyl

Administered IV, IM, or epidural; orally to cats Delayed onset of action and longer duration of

analgesia Used with a sedative it can prolong sleep times Expensive Schedule V drug (United States) and

unavailable in Canada


Opioid Agents: Nalbuphine

Kappa agonist and mu antagonist with greater antagonist properties than butorphanol Weak analgesic and sedative Used as a reversal agent for opioid agonists Fewer adverse effects

Not a controlled drug in the United States


Opioids as Postoperative Analgesics

Administered IM or SC before animal regains consciousness Injections repeated as necessary Alternative routes (IV, epidural, intraarticular,

transdermal patch) minimize adverse effects Disadvantages

Short duration of action Potential adverse reactions: respiratory depression,

bradycardia, excitement, apprehension, hypersalivation, mydriasis, excessive sedation, panting, increased sensitivity to sound, urinary retention, gastrointestinal effects


Opioids: Intravenous Infusion

Morphine, fentanyl, oxymorphone, hydromorphone, methadone, butorphanol

Provides continuous analgesia for constant, unremitting pain


Opioids: Intravenous Infusion (Cont’d)

Initial loading dose given to effect followed by same dose given over 4 hours through constant flow Drug may be added to a bag of fluids if an automated

infusion pump is not available Monitor patient frequently for adequate pain control,

excessive sedation, or adverse effects Adjust rate of administration according to patient response

Morphine (for example) can administered with lidocaine or lidocaine/ketamine to control severe pain


Opioids: Intraarticular Injection

Especially useful after elbow or stifle surgery Morphine diluted in saline instilled into joint

via catheter Immediately after joint closure Can be combined with a local anesthetic

(e.g., bupivacaine) Provides 8-10 hours postoperative analgesia


Opioids: Epidural Injection

Instillation of opioid into epidural space at lumbosacral junction To provide analgesia to hind limbs, abdomen,

caudal thorax, pelvis, tail Morphine is the most commonly used drug May be combined with an alpha2-agonist in large

animals Profound postoperative analgesia with long

duration of action


Opioids: Epidural Injection (Cont’d)

Instillation of an opioid into the epidural space at the lumbosacral junction Administer after induction of anesthesia, but

before surgical procedure begins Onset of action: 20-60 minutes Duration of action 6-24 hours Must be supplemented with general anesthesia for

surgical procedures Reposition animals every 2-4 hours to prevent

pulmonary atelectasis or prolonged pressure on superficial nerves


Opioids: Transdermal Use

Fentanyl transdermal patch Reservoir of fentanyl enclosed in plastic Attached to clipped skin and left in place for

several days Comes in various sizes

(25 mcg/hr; 50 mcg/hr; 75 mcg/hr; 100 mcg/hr) Large animals may require more than one patch


Opioids: Transdermal Use (Cont’d)

Provide convenient, long-term opioid administration Similar to IM oxymorphone injection but longer

duration of action Delay of action from 4 to 12 hours (cats) or 12 to

24 hours (dogs) as drug is absorbed through the skin

Apply patch at least 6-12 hours prior to the start of surgery

Supplement with another opioid or NSAID if patch isn’t applied until after surgery


Opioids: Fentanyl Patch

Use: Provide analgesia for postoperative pain and pain associated with trauma, burns, cancer, and painful abdominal conditions Amount of drug absorbed through skin varies

among animals Monitor for breakthrough pain and supplement as

necessary Monitor for fentanyl overdose

• Ataxia and sedation (dogs)• Dysphoria and disorientation (cats)

Remove patch if necessary


Opioids: Fentanyl Patch (Cont’d)

Heat may increase the amount of fentanyl absorbed Avoid using in animals with fevers Avoid contact of patch with external sources of

heat (e.g., hot water bottles)


Nonsteroidal Antiinflammatory Drugs

NSAIDs or nonsteroidal antiinflammatory analgesics (NSAAs)

Acetylsalicylic acid (aspirin) CarprofenAcetaminophen EtodolacMeloxicam Tolfenamic acidKetoprofen DeracoxibFirocoxib


Nonsteroidal Antiinflammatory Drugs (Cont’d)

Mechanism of action Efficacy: somatic and visceral pain (varies by

drug) Onset of action: 30-60 minutes Duration of effect varies with species Toxicity varies with species Analgesic and antiinflammatory properties vary by

drug Inhibit prostaglandin synthesis by inactivating COX

isoenzymes Metabolized in the liver; eliminated by the

kidneys and the gastrointestinal tract


Adverse Effects of NSAIDs

Prevent the production of beneficial prostaglandins along with the production of prostaglandins that mediate pain, inflammation, and fever

NSAIDs that inhibit the COX-2 enzyme but not the COX-1 enzyme produce the least adverse effects

The perfect NSAID is not available yet


Adverse Effects of NSAIDs (Cont’d)

Adverse effects vary with drug, species, breed, and individual animals Stomach ulcers, vomiting, gastrointestinal

bleeding, lack of appetite Gastrointestinal ulceration leading to hemorrhage Renal toxicity Impaired platelet aggregation leading to prolonged

bleeding time Liver damage Antagonist to several drugs prescribed for cardiac

disease and hypertension


Other Analgesic Agents

Opioids and NSAIDs are the most commonly used analgesics

Local anesthetics, alpha2-adrenergic agonists, and ketamine are also used as analgesics in special circumstances


Local Anesthetics as Analgesics

Used to prevent or treat postoperative pain Sprayed or injected at the site of injury or surgical

site or infiltrated around a nerve supplying the affected area

Desensitize the entire region (epidural or IV infusion)


Local Anesthetics as Analgesics (Cont’d)

Advantages Complete anesthesia of affected area Low toxicity Rapid onset of action

Disadvantages Short duration of action CNS and cardiac toxicity with repeated use


Alpha2-Adrenoceptor Agonists as Analgesics

Limited use in small animals Short duration of analgesic effect Profound sedative effect Adverse effects: respiratory depression, vomiting,

bradycardia, heart block, hypotension When used in low doses may potentiate opioid

effects and increase quality of postoperative analgesia

Produce significant analgesia via the epidural route alone or with other agents


Alpha2-Adrenoceptor Agonists as Analgesics (Cont’d)

Used in horses to provide sedation, muscle relaxation, and analgesia Xylazine, detomidine, romifidine Horses remain standing but may become ataxic Analgesia okay for moderately to severely painful

diseases or procedures Adverse effects

• Cardiovascular effects, respiratory effects, GI effects Reversal with alpha2-adrenoceptor

antagonists will also reverse sedation and analgesia


Ketamine as an Analgesic

Used as an adjunct to more potent analgesics (opioids, local anesthetics, alpha2-agonists) Doesn’t produce analgesia by itself MLK (morphine, lidocaine, ketamine) provides

intraoperative analgesia Blocks NMDA at the level of the spinal cord to

prevent windup Use a lower dose than the one used to

induce anesthesia


Ketamine as an Analgesic (Cont’d)

Adverse effects: dose-related effects rarely seen at analgesic levels Tachycardia Hypertension Seizures Postoperative delirium Increased intraocular and intracranial pressure Salivation


Corticosteroids as Analgesics

Strong antiinflammatory properties Decrease prostaglandin activity such as NSAIDs Don’t use concurrently with NSAIDs

Adverse effects Ulcerogenic Immunosuppression with long-term use Hyperadrenocorticism


Tramadol as an Analgesic

Nonopiate drug with activity at the mu receptor Also inhibits reuptake of norepinephrine and

serotonin Administered orally after patient has resumed

eating A postoperative alternative to opiates Can be administered at home

Don’t use concurrently with other norepinephrine or serotonin reuptake inhibitors (e.g., amitriptyline)


Tranquilizers and Analgesia

Tranquilizers are not considered analgesics May potentiate effects of opioids in anxious

patients Useful in calming the excitement sometimes seen

in cats and horses following opioid administration Cannot be substituted for opioids or other

analgesic agents


Multimodal Therapy

Use of more than one type of analgesic to relieve pain Pain is produced by several mechanisms Different drugs will target different mechanisms

along the pain pathway


Examples of Multimodal Therapy

Acetaminophen and codeine Oral treatment for moderate to severe pain in dogs

Fentanyl and meloxicam Administered at the same time to cats to provide analgesia

until the fentanyl patch takes effect Morphine and injectable NSAID (meloxicam or

carprofen) Administered at the end of surgery followed by oral NSAID

for 3 days MLK

Administered in IV fluids during surgery, decreases amount of inhalant anesthetic needed


Home Analgesia

Fentanyl patches Used sequentially for up to several months for

chronic pain (dogs and cats) NSAIDs

Long-term therapy of chronic painful conditions Oral morphine

Sustained-release tablet administered BID to effect

Tylenol with codeine (dogs) and butorphanol Tablet for mild-to-moderate pain

Tramadol


Nursing Care

Relieving patient discomfort will help pain control Keep patient and cage or stall clean and dry Comfortable bedding/quiet surroundings Opportunity to urinate and defecate Comfortable position

• May have to turn every 2-3 hours Reduce anxiety with toy or blanket from home Ophthalmic ointment in unconscious patients to

prevent corneal drying Comforting reassurance through touch and talking


Nonpharmacologic Therapies

Used in conjunction with or as an adjunct to pharmacological therapy Acupuncture Transcutaneous electric nerve stimulation Massage therapy Apply cold (acute injuries) or heat (chronic injuries) Physiotherapy Laser or magnetic therapy Homeopathic or herbal remedies

Health & Medicine

7. Analgesia