Nigel Campbell,     Raleigh, North Carolina

Opioids

Opioids, the primary drugs for treating pain in the critical patient, also provide mild to moderate sedation, depending on the agent. The most commonly used opioids are the pure mu agonists (morphine, hydromorphone, oxymorphone, and fentanyl) and the partial mu agonist, buprenorphine. Butorphanol, a kappa agonist and a mu antagonist, provides less analgesia but more sedation. Fentanyl, a potent analgesic, has a very short half-life and therefore should be administered as a constant rate infusion (CRI) or a transdermal patch.

Methadone is a mu-receptor agonist that also inhibits N-methyl-d-aspartate (NMDA) receptors. It has similar duration and action to morphine but produces less sedation and vomiting. Intramuscular injection can be painful in cats.

Tramadol is a weak mu-receptor agonist that also inhibits neuronal reuptake of norepinephrine and serotonin. There are reports of adequate analgesia being provided by oral tramadol (Lamont et al, 2008). Because of the risk of serotonin syndrome, tramadol should not be used in patients receiving monoamine oxidase inhibitors. Side effects can include sedation or dysphoria, especially in cats.

Buprenorphine is increasingly used in clinical practice. In addition to parenteral administration, it can be administered via the oral transmucosal route (OTM). This route has been demonstrated to provide analgesia in the cat at 0.02 mg/kg (Robertson et al, 2005). However, in the dog this dose has lower bioavailability and seems to provide little analgesia. A higher OTM dose (0.12 mg/kg) has greater bioavailability, and in a study of dogs undergoing ovariohysterectomy (OVH) it appeared to be an alternative for postoperative pain management when given immediately before anesthetic induction (Ko et al, 2011). However, drug cost and the volume that must be administered (in bigger dogs) may be concerns. Buprenorphine SR is an injectable, sustained-released (polymer) formulation that is designed to release buprenorphine over a 72-hour period; in cats undergoing OVH this appeared to have an efficacy and adverse effect profile comparable to twice-daily OTM administration of buprenorphine (Catbagan et al, 2011). There have been anecdotal reports of some dogs exhibiting dysphoria and anorexia when buprenorphine SR is used at higher doses.

Nonsteroidal Antiinflammatory Drugs

Nonsteroidal antiinflammatory drugs (NSAIDs) work by inhibiting cyclooxygenase (COX) and preventing the production of prostaglandins (PGs), which decreases inflammation to provide analgesia. NSAIDs have a longer onset of action (45 to 60 minutes) compared with opioids and most provide analgesia for an extended period (12 to 24 hours). When used in combination with opioids, NSAIDs can have a synergistic effect and provide improved analgesia compared with use of either drug class alone.

Side effects of NSAIDs include gastrointestinal ulceration, renal damage, and a decrease in platelet function. Accordingly, obvious contraindications to NSAIDs include gastrointestinal ulceration or bleeding, platelet dysfunction, renal dysfunction, and concurrent corticosteroid use. Furthermore, hypotension, intravascular volume depletion (from vomiting, diarrhea, hemorrhage, or other fluid losses), and congestive heart failure can also constitute relative or absolute contraindications because these disorders can compromise function of the kidneys and gastrointestinal tract. Thus NSAIDs are most safely used in normovolemic, hemodynamically stable patients. However, carprofen did not cause clinically relevant adverse effects in dogs anesthetized for fracture repair, even when it was administered before surgery or given to patients with trauma-induced alterations in renal function or hemostasis (Bergmann et al, 2005).

Numerous NSAIDs are available in veterinary medicine. Those most commonly used in dogs include carprofen, deracoxib, firocoxib, and meloxicam. Only carprofen and meloxicam are available in an injectable form, so these tend to be used more in hospitalized patients that cannot tolerate oral administration of drugs. Commonly used NSAIDs in the cat are carprofen, ketoprofen, and meloxicam. NSAIDs must be used with caution in this species as cats have a low capacity for hepatic glucuronidation, which can lead to accumulation. Because of this, cat doses should never be extrapolated from those used in dogs.