In the UK it is estimated that there are currently approximately 2.5 million ‘senior’ cats (Gunn-Moore, 2003). Historically, it has been reported that UK veterinarians were less likely to use analgesics in cats compared with dogs in the peri-operative period (Capner et al, 1999; Lascelles et al, 1999). This finding is not limited to the UK (Raekallio et al, 2003; Hugonnard et al, 2004; Williams et al, 2005). For example 24.3% of veterinarians did not use analgesics after orthopaedic surgery in cats, in spite of the recognition that such procedures cause moderate to severe pain (Dohoo and Dohoo, 1996). Reasons for this trend may include:
- The potential side effects of opioids and non-steroidal anti-inflammatory drugs (NSAIDs)
- Poorer recognition of pain in cats
- Paucity of licensed analgesics for use in cats (Lascelles and Waterman-Pearson, 1997)
- Unique metabolism of drugs in cats
- Difficulty in administering medication long term to cats
- The lack of species specific information (Robertson, 2009).
In the presence of a noxious stimulus, detection of acute pain by the central nervous system may result in protective functions leading to rest, recuperation, guarding or avoidance which serves to minimize further injury and allow tissue healing.
In situations where extensive trauma or chronic or prolonged pain is experienced, the pain pathway can become altered resulting in a significantly negative impact on quality of life far exceeding any protective role. In the event of unmanaged chronic pain, abnormal or unexpected behavioural changes can occur and result in considerable suffering (Muir, 2009).
Recognition of pain in cats
The behavioural signals that may indicate pain in cats may include (but are not limited to): changes in activity; agitation; aggression; altered appetite; altered interaction with family members; altered posture; changes in sleep pattern; loss of house-training; altered response to handling; vocalizing; and lameness (Muir, 2009).
Considering whether acute or chronic pain exists may have implications for the approach to analgesia. Cats in acute pain following trauma or surgery are often depressed, immobile, tense and try to hide (Robertson et al, 2009). Cats with abdominal pain frequently adopt a crouched, sternal posture, with their head down, elbows drawn back, stifles forward, abdominal muscles tensed, and back arched, and their eyes are often half-shut or ‘squinting’ (Robertson, 2009).
The presence of chronic pain should also be considered in the geriatric patient. Osteoarthritis (OA) is reported to be present in up to 90% of cats over the age of 12 years (Hardie et al, 2002) with the hips and elbows most commonly affected. Overt lameness is not a consistent sign in cats with OA; instead, affected cats show weight loss, depression, abnormal elimination habits, poor grooming, aggressive behaviour and/or a reduced ability to jump (Clark and Bennett, 2006). OA may be bilateral and the resulting lameness hard to detect, combined with the pet cat's leisurely lifestyle, chronic pain due to OA may go unnoticed and therefore untreated. Other common sources of chronic pain may include, long standing ocular, neoplastic, oral or skin disease (Robertson, 2009).
Organ systems and considerations for the geriatric patient
Although there is little correlation between physiologic and chronologic age, and each animal must be evaluated individually (Pettifer and Grubb, 2007), age-related changes do occur in organ systems once maturity has been reached. An animal may be considered to be geriatric once it has completed 75–80% of its expected natural lifespan and cats older than 12 years of age may be described as geriatric (Dugdale, 2010). Geriatric patients show physiological regression in organ functions or in their mechanisms of compensation (Neiger-Aeschbacher, 2007).
Renal considerations
Structural and functional changes in the renal vascular system lead to diminished perfusion in the ageing kidney. Combined with a decreased parenchymal mass, the ageing kidney is not only more susceptible to acute injury but also less equipped to fully recover as repair mechanisms decline with age (Schmitt and Cantley, 2008). With ageing, there is a primary loss of cortical kidney mass and functional nephron units. Total renal blood flow and glomerular filtration rate declines with age. This indicates that drugs relying on renal excretion may have prolonged elimination times in geriatric animals necessitating reduction in doses (Pettifer and Grubb, 2007).
Proteinuria (urine protein: creatinine ratio) and plasma creatinine have been shown to be useful predictive markers of the development of azotaemia and renal failure. These values should be included in geriatric screening programmes for cats (Jepson et al, 2009) and may be useful in monitoring those receiving ongoing analgesic medication.
Hepatic considerations
The mass of the liver decreases with advancing age leading to an overall decrease in hepatic function. Hepatic and splanchnic flow also reduce with age (Mosier, 1989). This acts to decrease drug clearance (Muravchick, 2000) which may act to prolong the half life of those drugs which rely solely on hepatic metabolism.
Cardiovascular considerations
In geriatric animals, cardiac output becomes more preload dependent, so to increase cardiac output relies on increased stroke volume in association with an increase in end-diastolic volume. For this reason, volume depletion during the peri-operative period is less well tolerated in geriatric animals than in younger animals (Thurmon et al, 1996). Age-related reduction in cardiac output results in reduced regional and organ blood flow, which in turn may result in reduced drug absorption capacity, drug hepatic metabolism and renal clearance capacity (Neiger-Aeschbacher, 2007).
Analgesic drug groups
Opioids
Opioids are commonly used in cats alone or in conjunction with acepromazine, benzodiazepines, or α2-agonists in clinical practice (Lamont, 2002). Table 1 summarizes dosing strategies for opioids in geriatric feline patients.
Pure μ-agonists, pethidine, morphine, and methadone, provide the greatest sedation but may also cause the greatest cardiovascular and respiratory depression (Carpenter et al, 2005), although these side effects are less pronounced in animals in pain.
Pethidine
Pethidine was, until recently, the only licensed pure μ-agonist available. It is an affective analgesic but only of relatively short duration (1–2 hours) (Robertson and Taylor, 2004). It is most commonly used to address acute pain in the peri-operative period.
Veterinary formulation: Pethidine 50 mg/ml solution for injection (Dechra Veterinary Products, Shropshire, UK).
Morphine
Morphine is a pure μ-agonist and also has effects at κ and δ opioid receptors. It is not licensed for veterinary use. Morphine is commonly used in the peri-operative setting to address acute pain, doses of 0.1-0.2mg/kg (intravenous (IV), intramuscular (IM)) have been shown to afford effective analgesia and no excitation has been associated with these doses (Robertson and Taylor, 2004).
Methadone
Methadone is a potent analgesic; it is a pure μ-agonist and also exerts antagonistic effects at the N-methyl-D-aspartate (NMDA) receptors. It has recently been licensed for veterinary use in dogs and is subject to strict controlled schedule drug regulations. In healthy cats undergoing ovariectomy, pre-operatively administered methadone (0.6 mg kg IM) provided effective analgesia for at least 4 hours after ovariectomy and did not produce adverse effects (Rohrer Bley et al, 2004). This is a higher dose than commonly used in veterinary practice where doses of 0.05–0.2 mg/kg subcutaneous (SC)/IM/IV are used in cats (Lamont and Matthews, 2007).
Veterinary formulation: Comfortan® 10 mg/ml solution for injection (Eurovet Animal Health, Cambridge, UK).
Fentanyl
Fentanyl is a μ-agonist with a short duration of action (20 minutes). It is not licensed for veterinary use. In the hospital setting, continuous infusions may be utilized during general anaesthesia to reduce the requirements of volatile agents in geriatric or debilitated patients. The infusion can be continued in the post-operative period (2–5 μg/kg/hour) and tailored to the cat's individual needs (Robertson, 2009). A loading dose is administered before the infusion is started (1–5 μg/kg IV). Davidson et al, 2004 demonstrated effective use of transdermal fentanyl patches (25 μg/hour) in healthy cats undergoing ovariohys-terectomy. Dose reduction for geriatric or debilitated patients may be achieved by reducing the exposed area of the patch by half (Davidson et al, 2004).
Buprenorphine and butorphanol
Buprenorphine and butorphanol may be quite useful in the geriatric animal, where concern for cardiopulmonary instability is present but mild sedation and analgesia are desired for the procedure (Carpenter et al, 2005).
Buprenorphine is a partial μ-agonist and causes minimal cardiovascular or respiratory depression (Tranquilli et al, 2005) enabling it to be a safe choice of analgesic in geriatric cats. Onset of analgesia is reported to vary depending on route of administration. IM injection is the only licensed route of administration.
The IV route provides analgesia within 30 minutes, having a peak effect after 90 minutes (Robertson et al, 2003). Onset of effect may be slightly longer, 45–60 minutes, with IM and SC dosing, with the effect lasting at least 6 hours (Robertson et al, 2003).
The transmucosal route has also been investigated in cats and shown to have almost 100% bioavailability in cats due to alkaline (pH 8–9) feline oral environment. A starting transmucosal dose of 20 μg/kg was shown to be as effective as IV administration and provides analgesia for up to 6 hours. This route of administration can be performed by owners for at home treatment (Robertson, 2009).
Veterinary formulation: Buprecare® 0.3 mg/ml injectable solution (Animalcare, York, UK), Bupreno-dale® 0.3 mg/ml solution for injection for dogs and cats (Dechra Veterinary Products, Shropshire, UK), Vetergesic® injection 0.3 mg/ml (Alstoe, York, UK).
Butorphanol is a κ-agonist–μ-antagonist. Al-Gizawiy and Rude (2004) showed inadequate analgesia afforded by butorphanol in cats undergoing ovario-hysterectomy. It may be useful as a sedative (0.1–0.2 mg/kg IM, 0.05–0.1 mg/kg IV) in severely debilitated animals to allow non-painful procedures such as imaging. Minimal adverse cardiovascular and respiratory side effects are associated with its use.
Table 1. Summary of opioid dosing
| Acute pain | Duration | ||
|---|---|---|---|
| Pure μ-agonist | Pethidine | 3.3 mg/kg IM | 1–2 hours |
| Morphine * | 0.05–0.2 mg/kg IM/SC (Lamont and Matthews, 2007) | 3–4 hours (Taylor et al, 2001) | |
| Methadone ** | 0.1–0.2 mg/kg IV/IM (Lamont and Matthews, 2007) | 4 hours | |
| Fentanyl * |
|
Single bolus duration 20 mins | |
| Partial μ-agonist | Buprenorphine | 0.01–0.02 mg/kg IM | Duration 2–6 hours (Robertson et al, 2003) |
| Buprenorphine | 0.02 mg/kg transmucosally ≡ | Duration 6 hours (Robertson, 2009) | |
| Agonist–antagonist | Butorphanol | 0.4 mg/kg IM/SC 0.1 mg/kg IV |
*Product not licensed for veterinary use or ≡ not licensed via the route described.
** Product not licensed for use in cats.
IM, intramuscular; SC, subcutaneous; IV, intravenous
Veterinary formulation: Torbugesic® 1% solution for injection (Pfizer, Kent, UK), Alvegesic® vet 10 mg/ml solution for injection (Dechra Veterinary Products, Shropshire, UK), Dolorex® 10 mg/ml injection (MSD Animal Health, Milton Keynes, UK).
Side effects of opioids
There are a number of possible side effects of opioids, and these are outlined below.
- Gastrointestinal: nausea (licking of the lips, apprehension, and salivation) and vomiting are features of opioid administration in many species (Robertson, 2009).
- Vision: in contrast to many other species, opioids cause marked mydriasis (dilation of the pupil) in cats. Resultant vision deficits may cause bumping into objects or startled behaviour when approached quickly. It is recommended to shield cats from bright light while their pupils are dilated. In research models, opioid-induced mydriasis does not correlate with the duration of analgesia (Robertson, 2009).
- Thermoregulation: hyperthermia has been reported following hydromorphone administration in cats (Posner et al, 2007; Niedfeldt and Robertson, 2006).
- Excitation or ‘mania’: rarely seen after opioid administration at analgesic doses in cats experiencing pain. Reports of adverse behavioural events were often associated with very high dosing regimens in pain free cats (Robertson, 2009).
NSAIDs
NSAIDs (Table 2) are known for their therapeutic reduction of fever, pain and inflammation via inhibition of prostaglandin synthesis. Prostaglandins formed via COX-1 pathways may be described as physiologically helpful, which is why selective inhibition of COX-2 pathways is a proposed feature of some of the newer NSAIDs. Disruption of physiologically useful prostaglandin production can cause gastrointestinal, renal and clotting dysfunction. Although this is a fairly simplistic description of NSAID pharmacological actions, NSAIDs should be used with caution in elderly cats and full haematological and biochemical analysis should be carried out before NSAID therapy is initiated, particularly if long-term therapy is indicated.
Table 2. Summary of NSAID dosing in the cat
| NSAID | Acute pain | Post-operative pain | Chronic pain |
|---|---|---|---|
| Carprofen | 4 mg/kg SC/IV single dose | ||
| Ketoprofen | 2 mg/kg IV/IM/SC od for up to 3 days consecutively | 1 mg/kg PO od up to 5 days | |
| Meloxicam | 0.2 mg/kg SC | 0.05 mg/kg PO for up to 4 days | First single dose 0.1 mg/kg PO, followed by 0.05 mg/kg PO od |
| Robenacoxib | 2 mg/kg SC | 1–2.4 mg/kg PO od up to 6 days |
SC, subcutaneous; IV, intravenous; IM, intramuscular; PO, peros; od, once daily
Renal perfusion may also be reduced following use of NSAIDs so they must be used very cautiously in elderly cats and their use is contraindicated in cats with pre-existing renal compromise or in hypovolae-mic states. Some NSAIDs rely on glucoronidation via hepatic metabolism and therefore plasma clearance may be reduced in cats (Lascelles et al, 2007) and not recommended for use in cats with hepatic disease.
Carprofen
Carprofen has been reported to be an effective analgesic when administered pre-operatively in healthy cats (Mollenhoff et al, 2005; Al-Gizawiy and Rude, 2004). However, it must be used cautiously in elderly cats and is contraindicated in the presence of hepatic, gastrointestinal or renal compromise. Lascelles et al (2004) recommend a reduced dose of 2 mg/kg in healthy cats (the labelled dose is 4 mg/kg).
Veterinary formulation: Rimadyl® SA solution for injection 50 mg/ml (Pfizer Animal Health, Kent, UK), Rycarfa® 50 mg/ml solution for injection in cats and dogs (Dechra Veterinary Products, Shropshire, UK).
Ketoprofen
Ketoprofen was shown to provide safe and efficacious analgesia for acute locomotor disorders in cats when used at a dose of 1 mg/kg per os for up to 5 days (Morton et al, 2011).
No studies have reported the use of ketoprofen in geriatric cats, but Lascelles et al (2004) recommend a reduced dose of 1 mg/kg for up to 3 days. Morton et al (2011) reported lower palatability of ketoprofen compared with meloxicam liquid formulation according to owner assessment.
Veterinary formulation: Ketofen® 1% injection or 5 mg tablet (Merial, Essex, UK).
Meloxicam
In the peri-operative setting, 0.2 mg/kg SC meloxicam has been shown to be effective in alleviating post-operative pain in cats undergoing hysterectomy (Benito-de-la-Víbora et al, 2008). Meloxicam does not have a prolonged half life in cats because it is metabolized by hepatic oxidative pathways, and this may be why it has achieved success for long-term use (Robertson, 2009) such as in cases of OA. Two studies reported subjective assessment of pain relief by owners of cats on long-term meloxicam for OA to be significantly improved (Gunew et al, 2008; Bennett and Morton, 2009). In 40 cats diagnosed with OA receiving long-term (mean treatment period of 5.8 months) meloxicam treatment at a dose of 0.01–0.03 mg/kg per os, 4% exhibited gastrointestinal upset but no deleterious renal effects were detected in the cats studied (Gunew et al, 2008).
Veterinary formulation: Metacam® 5 mg/ml injection, 2 mg/ml oral solution for cats (Boehringer Ingelheim, Berkshire, UK), Meloxidyl® 5 mg/ml injection, 0.5 mg/ml oral solution for cats (CEVA Animal Health, Bucks, UK). Flexicam® 5 mg/ml injection for dogs and cats (Dechra Veterinary Products, Shropshire, UK).
Robenacoxib
Robenacoxib is a highly selective and potent inhibitor of COX-2, which should result in reduced toxicosis caused by inhibition of COX-1 (King et al, 2011).
Veterinary formulation: Onsior® 20 mg/ml injectable solution, 6 mg/ml tablets for cats (Novartis, Surrey, UK).
α2-agonists
α2-agonists are not commonly used for their analgesic effect alone because of the profound sedation and cardiovascular depression that accompanies their use. The vasoconstriction and decrease in cardiac output associated with α2-agonists preclude their use in cats with cardiovascular disease or pre-existing hypovolaemia (Robertson, 2009). The α2-agonists may be considered for sedation and premedication in healthy geriatric animals because they are reversible and thus are not dependent on hepatic or renal clearance for recovery (Carpenter et al, 2005). These agents must be used cautiously at reduced doses (5–10 μg/kg IM).
Veterinary formulation: Medetomidine: Dorbene Vet® injectable solution 1 mg/ml (Pfizer, Kent, UK), Dormilan® 1 mg/ml solution for injection (Dechra Veterinary Products, Shropshire, UK), Medetor® solution for injection (Virbac Animal Health, Suffolk, UK), Sedastart® 1 mg/ml solution (Animal Care, York, UK), Domitor® 1 mg/ml solution for injection (Janssen Animal Health/Elanco, Hampshire, UK).
Local anaesthetics
Local anaesthetics may be used for local and regional nerve blocking techniques to allow reduction in anaesthetic agents used during surgery. Lidocaine provides 1–1.5 hour's analgesia and the total dose administered should not exceed 2 mg/kg. Bupivicaine is longer lasting and affords analgesia for up to 4–6 hours and total dose administered should not exceed 1–2 mg/kg (Robertson and Taylor, 2004). To provide analgesia before placement of IV catheters or venupuncture, a topical form of lidocaine and prilocaine (EMLA) can be applied, although systemic absorption does occur, plasma concentrations remain below toxic values after 15 mg/kg lidocaine applied topically (Robertson, 2009).
Additional analgesics
Tramadol
Tramadol is a centrally acting analgesic (Pyendop et al, 2008) and binds to μ-opioid, serotonin and adrenergic receptors (Robertson, 2009). Tramadol is not licensed for veterinary use
Acute pain
Where there is acute pain tramadol can be used 2–4 mg/kg twice daily (bid) per os (Pyendop et al, 2009; Robertson, 2009).
There are limited data available in the clinical setting, but tramadol has been reported to provide effective analgesia for soft tissue surgery in cats (Robertson, 2009). It is recommended that a reduced dose is used in cats with renal or hepatic impairment.
Chronic pain and post-operative pain
In cases of chronic or post-operative pain, tramadol can be used at 2 mg/kg bid per os dose and has been shown not to have detrimental effects on primary haemostasis and renal, liver or gastrointestinal function in adult cats (Brondani et al, 2009).
Good bioavailability (Pyendop and Ilkiw, 2008; Robertson, 2009) and peak concentration achieved within 45 minutes of oral administration make tramadol useful for post-operative analgesia after hospital discharge and also for treating chronic pain in cats.
Side efects
Mild sedation and euphoria have been reported with tramadol use in cats. Accurate division of tablets can make dosing difficult in cats.
Gabapentin
Gabapentin appears to be particularly effective in chronic, especially neuropathic, pain in cats where an increase in sensitivity has occurred, or where the pain appears to be excessive in relation to the lesion present (Lascelles and Robertson, 2010). Gabapentin is not licensed for veterinary use.
Note: some formulations of gabapentin contain xylitol which can be toxic to dogs.
Chronic pain
Gabapentin can be used to treat chronic pain at a dose of 2.5–10 mg/kg bid per os (Gaynor, 2009; Lascelles and Robertson, 2010).
Side efects
Sedation is one of the most common side effects of gabapentin and may occur as increased doses are used to address escalating pain with time. Abrupt withdrawal of gabapentin can result in rebound pain in which the patient may experience even more pain than before the initiation of gabapentin therapy (Downing, 2011).
Amantadine
Amantadine acts as an antagonist at central NMDA receptors and is recommended as an adjunct therapy for treating chronic pain. Amantadine is not licensed for veterinary use.
Chronic pain
Where there is chronic pain amantadine can be used at 2 mg/kg per os once daily (od) (Possi et al, 2006), or 3–5 mg/kg per os od (Lamont and Matthews, 2007).
Amantadine does not cause sedation and seems to be well tolerated (Downing, 2011). It may be combined with NSAIDs or gabapentin (Robertson, 2009).
Supportive care
Because geriatric animals have decreased thermoregulatory capacity, every effort should be made during the peri-anaesthetic period to keep them warm with warmed fluids, circulating water blankets, and forced air warmers (Carpenter et al, 2005) (Figure 1). Sense of smell and taste also decline with age and the provision of warmed and softened food may help to entice elderly cats to eat in the post-operative period.
Conclusion
The provision of appropriate analgesia for geriatric cats must be tailored to the individual patient needs and consideration of concurrent conditions which may affect drug metabolism is important. By using a multimodal approach to analgesia, doses of individual drugs can be reduced while achieving sufficient levels of analgesia which can be maintained in the longer term when required. Huge advancements have been made in provision of analgesia in the veterinary profession over the last decade and continuing education will ensure that all species benefit from improved awareness in this area of veterinary care.
Key Points
- There are numerous detrimental physiological and behavioural effects of pain.
- Consideration of the pain pathway may help to select drugs which target different stages of the pathway.
- Analgesia protocols must be based on individual patient needs and consideration of concurrent disease and organ system compromise.
- A multimodal approach to analgesia affords superior pain relief and allows individual drug doses to be lowered.
- Continuing re-assessment of the effectiveness of analgesia allows an opportunity to tailor protocols to ensure adequate pain relief provision, particularly in the presence of chronic pain.
- Attention to additional supportive care in the peri-operative period is essential for geriatric patients.
- To answer the CPD questions on this article visit www.theveterinarynurse.com Questions have been approved by Harper Adams University College