Information
When formulating an analgesic regimen for a particular animal, several factors need to be considered:
- What is the likely severity of pain, and what is its anticipated duration?
- Which drug or drugs should be administered, and at what dose rates?
- Are there any special factors that will influence the choice of analgesic, for example, the animal species, any pre-existing abnormalities and any particular features of the current project or the type of pain?
- What facilities are available for management of the animal? What level of post-operative care and monitoring of the animal is available? Can staff attend throughout a 24-hour period? Are there facilities for continuous infusion of analgesics?
Timing of analgesic administration
One of the most important advances in the control of post-operative pain has been the realization that the timing of analgesic intervention may have a significant bearing on the intensity of post-operative pain. Administering analgesics before surgery may help prevent CNS sensitisation to noxious stimuli, which can lead to increased pain sensation post-operatively (“premptive analgesia”). The clinical benefit of this approach has been questioned in people, and the emphasis is currently on “preventive analgesia” to ensure that pain relief is provided before the return of consciousness. This is clearly preferable to not administering analgesics until pain is experienced.
It is important to appreciate that a single dose of analgesic, administered prior to surgery, will not usually be all the analgesia that will be required. Additional analgesic medication will still be needed in the post-operative period, but this pain will be more easily controlled because preventive analgesia has been used. A further practical advantage of preventive analgesia is that it will often reduce the dose of anaesthetic drugs required, and by integrating analgesic therapy into a balanced anaesthetic technique, the potential adverse effects of anaesthesia can be improved, in addition to providing more effective pain relief.
‘Multi-modal’ pain therapy
Post-operative pain arises from the activation of a multiplicity of pathways, mechanisms and transmitter systems. Administering a single class of analgesic often fails to suppress all of these mechanisms, even when high dose rates are used. Multi-modal pain therapy advocates the use of several different analgesics to provide more effective analgesia. In humans, this concept has been widely adopted, and has the advantage that lower doses of each different analgesic can often be used, when they are given in combination. There are good experimental data in animals to support this concept,and some evidence for efficacy in alleviating post-operative pain in animals is now available. It is an easy technique to use, and the balance of evidence suggests it will be of benefit. For example, the use of an opioid such as buprenorphine can be combined with an NSAID such as carprofen. The opioid acts centrally to limit the input of nociceptive information into the CNS and so reduces central hypersensitivity. In contrast, the NSAID acts centrally to limit the central changes induced by the nociceptive information that does get through. In addition, the NSAID peripheral actions decrease inflammation during and after surgery and limit the nociceptive information entering the CNS, as a result of the inflammation. By acting on different points of the pain pathways, the combination should be more effective than either drug given alone. Adding a local anaesthetic to this regimen can provide additional analgesia by blocking specific nerve pathways and so further improve the degree of pain control.
Providing long-term pain relief
A number of clinical problems arise when analgesics are administered to control post-operative pain. The most important problem is the short duration of action of most of the opioid (narcotic) analgesics. Maintenance of effective analgesia with, for example, morphine may require administration every 1–4 hours, depending upon the species. Continuation of such a regimen overnight can cause practical problems. One method of avoiding this difficulty is to use buprenorphine as the analgesic, since there is good evidence in humans, rodents, rabbits and pigs that it has a duration of action of 6–12 hours, depending upon the dose administered. In clinical use in a wide range of animal species, it appears to provide effective pain relief for 4-8 hours, depending upon the dose administered.
Prolonged analgesia can also be provided by the use of slow-release patches that are placed on the animal’s skin. Both fentanyl and buprenorphine patches are available, and they have been used with some success in a range of species. The patches are manufactured for use in humans, so the rate of drug release varies in different animal species. Measurement of plasma concentrations of drugs has shown that considerable individual variation occurs. For this reason, it is best to consider these patches as providing basal analgesia, and to assess the animal regularly to ensure sufficient analgesia is being provided. Patches need to be placed on the skin for approximately 24 hours before adequate plasma concentrations of analgesic are attained.
Slow-release formulations of buprenorphine are now available commercially (see earlier), and these can provide effective plasma concentrations of analgesics for up to 3 days. These formulations may be particularly valuable when prolonged moderate to severe pain is anticipated.
Oral administration
The need for repeated injections of analgesics is time consuming and may be distressing to the animal, particularly smaller species that require firm physical restraint to enable an injection to be given safely and effectively. In addition, the need for repeated injections requires veterinary or other staff to attend the animal overnight. To circumvent this problem, the possibility of incorporating analgesics in food or water has been investigated. Unfortunately, several practical problems limit the use of this technique. Some animals eat and drink relatively infrequently, or may only do so in the dark phase of their photoperiod. In addition, food and water intake may be depressed following surgery, and this, coupled with wide individual variation in consumption, makes routine application of the technique difficult. If opioids are used, the high first-pass liver metabolism following oral administration requires that high dose rates are given, and this can represent a significant cost if all of the animals’ drinking water or food is medicated. Finally, there may be problems of palatability.
Since fluid consumption can vary both due to varying husbandry conditions and between different strains of animals both over-dosing as well as under-dosing is possible, so it is important to measure the animals’ actual fluid consumption. It is also important to provide effective analgesia by other means in the period before the animal commences drinking
Medication of the feed has also been suggested as a means of providing repeated dosing with analgesic, and palatable preparations of a number of NSAIDs are available. Administration of small quantities of medicated food does not avoid the need for repeated attendance overnight, but does remove the need for repeated subcutaneous or intramuscular injections in small rodents. Provision of analgesia with buprenorphine in flavoured gelatin (‘Buprenorphine Jello’) has been recommended as a means of providing post-operative pain relief in rats but it should only be used if a reliable pain assessment system is in place. With all medicated foodstuffs, rats are initially cautious of jelly pellets, but once a few pellets have been consumed, subsequent pellets are eaten as soon as they are offered. It is therefore advisable to commence administering pellets, which do not contain analgesic, 2–3 days before surgery. After surgery, analgesic-containing jelly can be given. The flavoured gelatin used is domestic fruit-flavoured jelly, reconstituted at double the recommended strength. Other highly palatable foodstuffs, eg Nutella have also been shown to be suitable vehicles for oral analgesic administration.
Additional considerations in pain relief
Although the use of analgesic drugs remains the most important technique for reducing post-operative pain, the use of these drugs must be integrated into a total scheme for peri-operative care. Pain relief in the immediate recovery period can be provided by including an analgesic drug in any pre-anaesthetic medication. Alternatively, if a neuroleptanalgesic combination has been used to produce anaesthesia, it can be reversed by the use of buprenorphine, nalbuphine or butorphanol, rather than naloxone. These agents have been shown not only to reverse the respiratory depressant effects of opioids such as fentanyl but, in contrast to naloxone, to provide effective prolonged analgesia.
The expertise of the surgeon can also greatly influence the degree of post-operative pain. A good surgical technique which minimizes tissue trauma and the prevention of tension on suture lines can considerably reduce post-operative pain. The use of bandages to pad and protect traumatized tissue must not be overlooked and forms an essential adjunct to the use of analgesic drugs.
Aside from measures directed towards alleviating or preventing pain, it is important to consider the overall care of the animal and the prevention of distress. Distress is used in this context to describe conditions which are not in themselves painful, but which are unpleasant and which the animal would normally choose to avoid. For example, recovering from anaesthesia on wet, uncomfortable bedding in a cold, unfamiliar environment would be likely to cause distress to many animals. It is essential to consider the methods described for the control of pain, in conjunction with the techniques discussed earlier in this chapter, aimed at providing good post-operative care.