Pain management for small animal clinical patients: Critical care and peri-operative analgesics (Proceedings)

Pre-emptive Analgesia.

Balanced Analgesia

Dose to Effect

Clinical Uses of Opioids

• Antitussive: cough suppressant action of opioids

• Pre-anesthetic medication, analgesia and sedation

• Induction of anesthesia: sole drug for some species (humans), valuable adjuvant for veterinary patients

• Intraoperative analgesia: reduced anesthetic requirement, decrease complications and improve outcome

• Postoperative pain relief: improved outcome and quicker recovery, reasonable post-op comfort for all

• Critical care adjuvant: basic analgesia, facilitates mechanical ventilation, tolerance of tracheal tube, and other supportive measures. Providing good analgesia improves clinical outcome for critically injured patients.

Opioid Analgesics and Recommended Doses

Morphine

• Dog: 0.25 - 0.5 mg/lb (0.5 - 1.0 mg/kg) IM, SC

• Cat: 0.025 - 0.05 mg/lb (0.05 - 0.1 mg/kg) IM, SC (Very useful at 1/10th the dog dose)

• Duration: 4-6 hours

• Sedation accompanying analgesia

• Vomiting, diarrhea, and bradycardia may occur

• Hypotension and bronchoconstriction (histamine release, especially with IV use) may occur

Meperidine (Demerol)

• Dog: 1-5 mg/lb (2-10 mg/kg) IM, SC

• Cat: (usually effective, avoid high doses)

• Duration: 0.5-1 hour

• Mild sedation

• Rarely histamine release and hypotension

• Cardiac and gastrointestinal effects are relatively minimal

Hydromorphone

• Dog: 0.025-0.05 mg/lb (0.05-0.1 mg/kg) IM, SC, IV

• Cat: 0.01-0.025 mg/lb (0.025-0.05 mg/kg) IM, SC, IV

• Duration: 4 hours

• Panting, vomiting, diarrhea, bradycardia may occur

• Dose-dependent sedation or excitement

Fentanyl

• Dog and Cats: 2-10 micrograms/kg/hr as a constant rate infusion after IV loading dose of 2-10 micrograms/kg

• Rapid onset and short duration

• Procedural uses and as a CRI for sustained and titratable analgesia in critical care

• May be combined with lidocaine CRI

Mixed-Acting Agonist-Antagonist Opioid Analgesics:

Pentazocine (Talwin)

• Dog: 1-2 mg/lb (2-3 mg/kg) IM

• Cat: same as dog dose

• Only mild analgesia

• Minimal systemic effects

• Narcotic reversal, ceiling effect

Butorphanol (Torbutrol, Torbugesic, Stadol)

• Dog: 0.1-0.2 mg/lb (0.2-0.5 mg/kg) IV, IM, SC

• Duration: 1-2 hours

• Antitussive effect (often desirable)

• Minimal systemic effects

• Narcotic reversal (partial reversal)

• "Ceiling effect" – very limited analgesia, useful for mild sedation

• Cat:(same as for dog, except for a longer duration of action 2-4 hours)

Nalbuphine (Nubain)

• Dog: 0.2-1.0 mg/lb (0.5-2.0 mg/kg) IM, IV

• Limited effectiveness - "ceiling effect"

• Minimal sedation

• Minimal systemic effects

• Narcotic reversal, ceiling effect

Partial Agonist Opioid Analgesics

Buprenorphine (Buprenex, Temgesic)

• Dog: 0.005-0.01 mg/lb (0.01-0.02 mg/kg) IM, SC

• Cat: 0.005-0.01 mg/lb (0.01-0.02 mg/kg) IM, SC, and oral mucosal with excellent uptake

• Duration: 6-8 hours (slow onset, even with IV injection, 30-40 minutes)

• Complications: Minimal systemic effects, some "ceiling effect", but rather potent analgesia.

Non-Opioid Analgesics

Tramadol (Ultram, Ultracet, etc.)

• Mild opioid, non-NSAID analgesic with mu-opioid binding activity and interference with both serotonin storage and norepinephrine re-uptake. Analgesic action exceeds mu receptor binding characteristics. First metabolite has greater mu-binding than parent compound. Not a DEA controlled substance. Tramadol may be effective where a weak opioid such as codeine would be chosen. Tramadol dose in Dogs: 1-4 mg/kg PO q 8-12 h for 5-7 days. 50mg tablets available in the US. Call Besse medical 1-800-477-7119.

Ketamine (Ketaset, Ketaset, Ketalar)

• Very low doses (actually sub-anesthetic, "sub-psychogenic" doses) potentiate opioid analgesics.

• The use of these very low doses, in balanced analgesic combinations, is a relatively new strategy. Dog or Cat doses: 0.01-0.5 mg/lb (0.02-1 mg/kg) IM, SC, PO, combined with opioids, etc.

• "Cataleptic" effects are minimal or absent at these low doses. Duration of 4-6 hours.

• CRI: loading dose 0.5-2.0 mg/kg, CRI at 2-10 micrograms/kg/min

Dex-Medetomidine (DexDomitor)

• Procedural analgesia, marked sedation. Standard dose is scaled to BSA (see box label).

• We use "micro-dose" DexDomitor method: DexDomitor (5-10 microgram/lb, 2.5 to 5 microgram/kg) IM or IV, combined with Torbugesic (0.1-0.2 mg/lb, 0.2-0.4 mg/kg) IM or IV.

• Reversal with Antisedan (by IM injection only) leaves the mild Torbugesic effect intact.

• Marked hemodynamic effects. Indicated for young, healthy, "exercise-tolerant" patients.

• Shorter duration and less need for reversal of DexDomitor relative to Domitor may be due to actions of Levo-Domitor in the previous formulation.

Xylazine (Rompun, Anased)

• Procedural analgesia (with marked sedation).

• Dog or Cat: 0.05-0.5 mg/lb (0.1-1.0 mg/kg) IM, SC, IV

• Duration: 15-60 minutes

• Moderate to marked sedation

• Emesis may occur

• Reversal with yohimbine or Antisedan

• Marked hemodynamic effects. Indicated for young, healthy, "exercise-tolerant" patients.

Lidocaine CRI

• Pro kinetic, reduced dose of other analgesics, possible anti-inflammatory action

• Loading dose 1-2 mg/kg, CRI at 25-100 micrograms/kg/min

• Easy set-up method: 68 cc of 2% lidocaine added to liter bag of IV fluid (or 34 cc lidocaine added to a 500 cc bag) administered at 1cc/pound/hour will provide 50 micrograms/kg/min

• Adjust rate between 0.5 and 2.0 cc/lb/hr to give lidocaine cri at 25 to 100 mcg/kg/min

• Reduce or discontinue if clinical signs of intolerance or overdose toxicity occur: nausea, CNS stimulation (twitching or seizures)

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Related Analgesics

• Perioperative risks of renal damage may be reduced by the appropriate administration of IV fluids before and during anesthesia to maintain blood pressure and renal blood flow. GI irritation may be subject to great individual variation. Patients should be monitored for development of intolerance and side effects as well as for changes in efficacy. Some of these NSAIDs are listed for historical reference only!

Meclofenamic Acid (Arquel) (Meclomen)

• Dog: 0.5 mg/lb (1.1 mg/kg) PO q 24 h Short-term use only

• Recommended for medical management of orthopedic conditions, e.g. hip dysplasia

• Complications reported with chronic administration: vomiting, tarry stools, mucosal erosions, leukocytosis, and decreased hemoglobin

Ketoprofen Tablets and Injectable

• Dog or Cat: 0.5-1 mg/lb (1-2 mg/kg) q 24 hours, IV (dogs only), IM, SC, PO initially, then reduce this dose by ½ for subsequent doses

• Mild to moderate pain

• Recommended for not more than five days in dogs. Use may be limited to one day in cats.

• Complications may include GI irritation, ulcers, and renal damage.

Carprofen (Rimadyl)

• Dog: 1mg/lb q12h (or 2 mg/lb q24h) per OS. Cat: 1 mg/lb q12-24h, 1-2 doses only

• Newer NSAID with greatly reduced GI toxicity.

• Relatively specific for COX-2 (anti-inflammatory) effects.

• Oral formulation available in 25, 75, and 100mg caplets or chewable tablets.

• Injectable carprofen 2mg/lb (4 mg/kg)

Etodolac (Etogesic)

• Dog: 4.5-6.8mg/lb (10-15 mg/kg) q24h per os.

• Newer NSAID with reduced GI toxicity.

• Relatively specific for COX-2 (anti-inflammatory) effects.

• Available in 150 and 300mg scored tablets.

Deracoxib (Deramaxx)

• Dog: 1-2 mg/kg/day as single daily dose for OA; or at 3-4 mg/kg/day as a single daily dose not to exceed 7 days, for post operative inflammation and pain

• "Cox-2 specific" action

• Flavored tablets.

Tepoxalin (Zubrin)

• Dog: 10-20 mg/kg on first day, then 10 mg/kg daily for OA or postoperative pain

• Rapidly disintegrating tablets (Redi-tabs)

• "Dual-pathway" inhibition of Cox/Lox. A different approach to the Cox-1/Cox-2 dogma on side effects of NSAIDs

Meloxicam (Metacam)

• Dog: oral (flavored) liquid, 0.2 mg/kg on day one, then 0.1 mg/kg daily on food

• "Out-sells Rimadyl in Canada at 5:1" Work down to lowest effective dose.

• Extensive clinical experience in Canada and EU, including the injectable formulation

• Cats: 0.3 mg/kg (0.14 mg/lb), injectable by subcutaneous route, single dose

• Oral meloxicam for cats (extra-label): Recommended often for cats at one drop q24-48 hrs after loading dose of two drops. Chronic use is controversial but recommended by some experts. (Little research data as yet. Risk of renal toxicity.)0.1mg/kg as single dose Day 1; 0.05mg/kg as single dose Days 2,3,4; 0.025mg/kg as single dose on Days 5,6,7 and thereafter q48h

Firocoxib (Previcox)

• Dog: Chewable tablets, 5 mg/kg (2.27 mg per pound) every 24 hours orally, with or without food. Available as 57 mg and 227 mg tablets. Selective inhibition of cyclooxygenase-2 (COX-2).

Other NSAIDs

• Many available. Toxic side effects can be prominent. Many reports warn of G.I. toxicity. Considerable patient-to-patient variation in susceptibility to toxic effects. Anti-inflammatory and analgesic effects are also quite individual (as in human patients). G.I. protective agents (e.g. misoprostol) can be beneficial.

Misoprostol for GI Protection

• Misoprostol (Cytotec) can be given to dogs or cats at 2-5 mcg/kg orally (once a day in cats, twice daily in dogs). It is used to increase tolerance to NSAIDs by reducing GI ulceration. Toxicity/side effects are anorexia and hepatopathy. Liver function testing (or liver enzyme analysis) should be performed monthly with misoprostol use (especially if misoprostol and NSAIDs are administered concurrently).

Acetaminophen (Tylenol, etc.)

• Analgesic and antipyretic for dogs, but not anti-inflammatory.

• Dog: 4.5-6.8mg/lb (10-15 mg/kg) q8h per os.

• Lacks GI toxicity. Can be most useful for dogs in opioid combinations, particularly for cancer pain, but also popular for postoperative use as Tylenol # 3 or #4.

• VERY TOXIC FOR CATS!

Acetaminophen Toxicosis in Cats

• Clinical Signs: cyanosis, dyspnea, facial edema, depression, and emesis

• Etiology: glucuronyl transferase deficiency (relative to other species)

• Therapy: Avoid stress!! If recent ingestion - induce vomiting Activated charcoal (2gms/kg) along with a saline cathartic, e.g. sodium sulfate (0.5 mg/kg) as a 20% slurry. Oxygen ASAP if cyanotic, but without adding further stress. Acetylcysteine (Mucomyst, Mucosol) 140 mg/kg PO or IV, and repeat at 70 mg/kg q6h for 36 hrs (seven treatments). Ascorbic acid 30mg/kg orally or parenterally with the acetylcysteine. Fluid therapy - lactated Ringer's solution. Continued intensive care and physiological support.

• (See: Cullison, R.F., Comp. Cont. Ed. 6(4): 315-320, April 1984.)

Epidural Analgesia and Anesthesia

Spinal or epidural opioid analgesia has been well described and proven effective in veterinary medicine. Epidural morphine analgesia is widely used in referral and academic centers and is increasingly popular as a method for providing long-lasting profound analgesia. The technique is rather simple, easily accomplished with basic clinical skill, and can be very cost-effective for providing substantial analgesia.

A relatively very small dose of morphine (0.1 mg/kg) is administered by epidural injection after induction of general anesthesia but prior to the surgical procedure. Effective pain relief persists into the following day (12 - 24 hrs) and is accompanied by a blunting of deleterious post-operative increases in stress hormones and the metabolic response to surgery. Combinations of morphine and bupivacaine provide the greatest analgesic effect.

Anatomical landmarks for Lumbosacral Epidural Injection

• Iliac crests, dorsal midline, and lumbar vertebral spinous processes

• For epidural injection, patients are under anesthesia and positioned in either sternal or lateral recumbency based on personal preference and best recognition of anatomic landmarks.

Dose Recommendations

• Morphine* 0.1 mg/kg

• Diluted to total volume of 0.2 ml/kg (Maximum of 6 ml for dogs and 1.5 ml for cats) using:

• Saline

• (or) Lidocaine (2.0%)

• (or) Bupivacaine (0.5 %)

Duration of analgesia

• 12-24 hrs.

Contraindications

• Local infection

• Neurological dysfunction

• Marked obesity (increased difficulty)

• Hypovolemia / Hypotension (avoid the local anesthetics)

Preservative-free morphine (e.g. Duramorph), designed for epidural use, is the best-recommended product. With the preservative-free morphine preparation, cost is increased. We currently do use the preservative-free morphine, usually in combination with either saline or 0.5% bupivacaine. The Duramorph preparation is at a concentration of 1.0 mg/ml. We administer 1 cc Duramorph per 10 kg body weight (0.1 cc/kg) mixed with either saline or bupivacaine, also at 1 cc per 10 kg, for a total volume of 2 cc per 10 kg, with a maximum total volume of 6 cc. The 30-pound dog in this illustration would receive 1.4 cc of Duramorph mixed with 1.4 cc of either saline or bupivacaine.

Combinations of opioids, alpha-2 agonists, and local anesthetics are becoming popular (once again) for epidural regional analgesia/anesthesia in various large animals including horses, cattle, and llamas.

Fentanyl Patches for Sustained Analgesia

Trans-dermal uptake of sustained-release fentanyl from a patch applied to the skin can provide long-term analgesia. This relatively new technology has now moved from the management of cancer pain in human patients to veterinary care where it is useful for sustained analgesia in animals with significant trauma, e.g. multiple fractures after vehicular trauma, as a portion of the management of post-operative pain, and in some cancer patients. Fentanyl patches can be very useful in cats as well as dogs.

The fentanyl patches sold as Duragesic from Janssen. They are available in different rates of drug delivery: 25, 50, 75, and 100 microgram/hour. Fifty mcg patches have been reported effective for small and medium size dogs. The 25mcg patches have been used extensively in cats. The behavioral effect of dysphoria and dementia may be unacceptable in some animals and may require tranquilization or removal of the patch. Uncovering only half of the barrier layer before application has been used in an attempt to reduce the dose, and minimize this problem, particularly in smaller dogs and in smaller cats, but is unreliable.

Patches are applied to clipped skin in an area that the animal cannot reach, such as the dorsal neck or the interscapular area of the dorsal midline. Uptake is somewhat variable among patients and clinical efficacy may be related, in part, to differences in uptake of fentanyl. Onset of analgesia is probably several hours after application of the patch. Hence, for operative or traumatic pain, some other drug should be used initially to provide analgesia. It is very important that the patient is prevented from damaging or ingesting these patches or the contents. Be aware that application of a heating pad, as during surgery, can greatly increase uptake of the drug with significant overdose possible. Duration of effectiveness is roughly four days.

Fentanyl can be a highly abused opioid and there have been reports of clients diverting fentanyl patches from their animals for drug abuse/diversion purposes. Some clinicians find the fentanyl patches a very useful part of managing cancer pain in outpatients, including the terminally ill. It is important to emphasize the potential dangers and the importance of protecting other pets and children from ingestion or other possible exposures. Expended (used) patches still contain fentanyl, and should be handled with care. Duragesic Patches are approved for use in human patients only. All veterinary use is strictly off-label.

Analgesic CRI (constant rate infusion)

CRI Options for Analgesia

• Lidocaine

• Low-dose ketamine

• Fentanyl

• Morphine

• Combinations of analgesics (e.g. lidocaine plus fentanyl cri

Adjunctive Analgesics

• Tramadol 4-6 mg/kg q 8 hours.

• Gabapentin: 3-10 mg/kg q 6-12 hours.

• Amantadine 3-5 mg/kg q 24 hours