2 Oct 2017
Jo Murrell discusses how to assess and quantify pain, and reports on advances made in managing this through analgesia.
Jo Murrell
Job Title
Figure 1. Palpating around the wound is pivotal to recognising unmanaged pain in cats and dogs.
Adequate pain management around the time of surgery or trauma is pivotal to ensuring the highest standard of care to patients.
Data tells us that provision of analgesia for routine surgeries in cats and dogs has significantly increased in the past 20 years (Capner et al, 1999; Hunt et al, 2015a), with approximately 98% of respondents in an analgesia survey of UK vets administering NSAIDs for neutering in 2013. Improvements in analgesia provision may relate to greater education of vets about the need for perioperative analgesia and the wider range of licensed analgesic drugs available compared to 20 years ago.
This article will focus on developments in pain assessment and advances in strategies to provide acute pain relief to cats and dogs.
All animals should receive analgesic drugs around the time of surgery; therefore, one could argue incorporating pain assessment into daily practice is unnecessary. On the other hand, animals are individuals and have differing requirements for analgesia, even after similar surgeries. Therefore, pain assessment is a prerequisite to the provision of adequate pain relief to all animals.
A gold standard approach is to assess pain, using a validated pain scoring tool, in all animals at frequent intervals after surgery and tailor analgesia administration to pain level. This is the best approach to avoid under or over-administration of analgesics and analgesic drug-related side effects. Pain assessment using modern validated tools only takes approximately five minutes per patient and should be achievable even within a busy practice setting. Pain assessment is a task best carried out by VNs most familiar with the cats and dogs in their care, and who are, therefore, better able to detect changes in behaviour related to pain.
The team at the University of Glasgow School of Veterinary Medicine has fundamentally changed our ability to quantify pain with the development of composite pain scoring tools for dogs (Holton et al, 2001) and cats (Reid et al, 2017). Composite tools take into account both the affective and emotional components of pain, and have replaced unidimensional scales, such as simple descriptive or numerical rating scales that focus solely on the intensity of pain. Taking into account the affective or emotional dimension of the pain experience is essential for adequate pain management.
The Glasgow composite pain scale for dogs can be freely downloaded (http://bit.ly/2vP0Swc) and requires the observer to assess the dog from outside the kennel to determine demeanour, then interact with the patient to assess mobility (if possible) and detect the presence of hypersensitivity to pain around any wound or painful area (secondary hyperalgesia; Figure 1). Secondary hyperalgesia is a cardinal sign of central sensitisation and upregulation of the pain pathways; therefore, identification on hyperalgesia is an indication that aggressive pain management is necessary.
The main disadvantage with the scoring tool is it differentiates poorly between sedation and pain; dogs that are very sedated can generate high scores with the tool and this can be misleading unless a “sense checker” is in place during score interpretation.
A big advantage of the tool is that the intervention criteria for requirement for rescue analgesia has been determined (Morton et al, 2005). Dogs scoring >4 out of 20 (non-ambulatory) or >5 out of 20 (ambulatory) require additional analgesia. Often a top up of methadone 0.1mg/kg is sufficient for these patients in the first instance.
The Glasgow composite pain scale for cats can also be freely downloaded (http://bit.ly/2xfwDSv), and has a similar look and feel to the dog assessment tool, which is advantageous if you are familiar with the dog tool and want to start using the cat tool in your practice. However, unlike the dog tool, it also incorporates two questions relating to facial expression (Holden et al, 2014); documenting both changes in muzzle/lip area and ear position. This is based on the robust identification of changes in facial expression, with pain in other species leading to the development of “grimace scales” for mice, rats, rabbits and horses (Langford et al, 2010; Sotocinal et al, 2011; Keating et al, 2012; Dalla Costa et al, 2014).
The maximum possible score for the cat scale is 20 and intervention analgesia is required when cats reach a score of 5 or more out of 20; similarly, methadone 0.1mg/kg or buprenorphine 20µg/kg is often suitable to treat unmanaged pain in cats reaching the intervention criterion.
Preventive analgesia is a new concept that has replaced pre-emptive analgesia as a goal for perioperative analgesia regimens (Katz et al, 2011). It aims to reduce sensitisation (peripheral and central) or upregulation of the pain pathways induced by noxious perioperative stimuli; therefore, it relies on both timing of analgesia administration (giving analgesics early) and giving analgesics for a long enough period of time to prevent upregulation of the pain pathways that may occur during the postoperative healing phase before the resolution of inflammation.
All perioperative analgesic regimens should adopt a preventive approach, although limited data exists to support decision making about how long to continue analgesic administration for after surgery. In cats undergoing neutering, changes in behaviour have been documented for three days after surgery, suggesting analgesia should be provided for this time period after neutering and it is likely at least a similar time period is appropriate for dogs (Väisänen et al, 2007).
Opioids remain the backbone of acute pain management in cats and dogs because they are licensed, efficacious and safe when used at clinical dose rates in animals in pain. Good evidence exists that methadone provides superior analgesia compared to buprenorphine for dogs undergoing orthopaedic surgeries (Hunt et al, 2013) and ovariohysterectomy (Shah et al, 2016); therefore, stocking methadone in your practice is fundamental to adequate pain provision. Fentanyl has been licensed for use in dogs and substantial data exists describing the use of fentanyl in cats (Ambros et al, 2014).
No studies are available comparing analgesia provided by fentanyl or methadone in dogs or cats, but pharmacologically and clinically fentanyl provides superior analgesia to methadone and is a useful drug to have available to treat severe pain. It is short-acting (a single dose of 5µg/kg to 10µg/kg IV provides analgesia for 10 to 15 minutes) and, therefore, can be used intraoperatively as a bolus to provide additional analgesia to combat brief nociceptive stimuli. However, it is also amenable to administration by continuous rate infusion (CRI; Sano et al, 2006), both intraoperatively to reduce the dose of inhalant agent to maintain anaesthesia (Williamson et al, 2017) and postoperatively.
When fentanyl is administered as a bolus or by CRI during anaesthesia it is important to monitor heart rate and respiratory function, as opioids can cause a clinically significant bradycardia and respiratory depression when administered to anaesthetised patients. Bradycardia associated with hypotension (mean arterial blood pressure <60mmHg) can be managed with atropine or glycopyrrolate, while respiratory function should be monitored continuously using capnometry.
Respiration should be supported by intermittent positive pressure ventilation when enditidal carbon dioxide tension is >60mmHg and the patient is at an appropriate depth of anaesthesia. Postoperatively, fentanyl at doses between 1µg/kg/hour to 5µg/kg/hour can be extremely useful to manage moderate to severe pain. Respiratory depression and bradycardia are not problematic in awake patients, but fentanyl should be administered using a controlled infusion apparatus (such as a syringe driver) to ensure accurate dosing of this potent and efficacious drug.
Administration of NSAIDs is also a key component of acute pain management drug regimens. A myriad of different NSAIDs are available for administration to dogs, with fewer options for cats. In dogs, no evidence supports either superiority in terms of efficacy (Leece et al, 2005; Gruet et al, 2011; 2013) or safety (Hunt et al, 2015b) of one NSAID over another for the management of acute post-surgical pain.
A single study compared robenacoxib and meloxicam in cats undergoing ovariohysterectomy and found marginal superiority of robenacoxib over meloxicam for one secondary outcome measure, although all cats were adequately analgesed with both drugs (Kamata et al, 2012). Similarly to dogs, no data supports greater safety of any one NSAID than another in cats (Hunt et al, 2015b), although injectable agents were associated with significantly greater side effects than orally administered agents. This may reflect the fact injectable agents are more likely to be administered around the time of anaesthesia.
Optimal timing of NSAID administration remains controversial, with pros and cons cited for preoperative versus postoperative administration. Due to the effect of NSAIDs to inhibit the production of renal prostaglandins, a precautionary approach is recommended. Do not administer NSAIDs to animals preoperatively unless blood pressure is measured intraoperatively and actively managed to prevent hypotension – avoid in patients at risk of significant haemorrhage or that have cardiovascular compromise where hypotension during anaesthesia is likely.
Local anaesthetic techniques are becoming increasingly used as part of multimodal analgesia regimens, although they are still relatively underused in first opinion veterinary practice (Hunt et al, 2015a).
Nerve location using electrical stimulation (such as a nerve stimulator) is extremely helpful to facilitate placement of some peripheral nerve blocks (such as brachial plexus or femoral and sciatic nerve blocks), but dental (maxillary and mandibular) nerve blocks and epidural administration of drugs should be well within the reach of first opinion practitioners to optimise pain relief in surgical patients.
de Vries and Putter (2015) wrote an excellent article that includes a description and diagrams of how to carry out dental nerve blocks in cats.
Simbadol (Zoetis) is a long-acting immediate release preparation of buprenorphine licensed in the US for the control of surgical pain in cats. It is licensed to be administered subcutaneously one hour before surgery and may be repeated once daily for three consecutive days.
The concentration of buprenorphine in Simbadol is significantly higher than the concentration of buprenorphine preparations available in the UK at 1.8mg/ml and the dose administered is also significantly greater at 0.24mg/kg once daily. It is likely the high dose, high concentration preparation leads to the 24-hour duration of action of the drug.
No studies in the public domain describe the use of Simbadol in cats; therefore, efficacy is difficult to evaluate objectively, although studies held on file documenting efficacy of Simbadol against placebo in 200 cats undergoing orthopaedic and soft tissue surgery are described on the Zoetis US website (http://bit.ly/2eQ0mHq).
It is unknown whether Simbadol will be licensed in the UK, but, should it become available, it would be expected to significantly increase our ability to provide adequate postoperative pain management to cats, particularly after they are discharged home where a single dose in the veterinary practice could provide 24 hours’ analgesia in the home environment.
Nocita (Aratana) is an extended release formulation of bupivacaine licensed in the US for local infiltration into the wound after cranial cruciate ligament surgery in the dog. To provide a longer duration of anaesthesia than bupivacaine hydrochloride or other local anaesthetics, the bupivacaine is an encapsulated liposomal formulation.
The multivesicular liposome particles are made up of a honeycomb-like structure consisting of many nonconcentric compartments that contain bupivacaine for gradual local release over an extended period of 72 hours. Limited data is available to show efficacy of the preparation after stifle arthrotomy in dogs (Tomas et al, 2015) and unilateral onychectomy in cats (Enomoto et al, 2017). It is unknown whether it will be licensed in the UK.
Great advances have been made in perioperative analgesia provision to cats and dogs over the past 20 years that will have, undoubtedly, had a significant impact to improve animal welfare. The licensing of fentanyl in the UK has increased the ability to manage moderate to severe pain in veterinary patients, particularly when used in combination with NSAIDs and local anaesthetic techniques.
If long-acting bupivacaine and buprenorphine are licensed for use in the UK in the future it would significantly expand our repertoire of drugs available for pain management, which would be of benefit to veterinary patients.
