Analgesic techniques in small-animal pets is challenging because of the inability to communicate with the patient. While much progress has been made regarding research techniques to investigate the safety and efficacy of various drugs, these studies still have deficiencies. Three common problems are (1) the subjective outcome measures that many studies depend upon; (2) the results of studies generally address the average patient, not the individual patient; and (3) studies rarely address the caregiver placebo effect. Another setback in veterinary medicine is that many drugs used for people are directly translated to use in animals without proper investigation of the pharmacokinetics and pharmacodynamics of the drug in the proper species; and even if these data are available, they are commonly ignored. These problems are magnified when our profession addresses analgesia in zoo and wildlife animals.
Since it is unlikely that detailed analgesic drug pharmacokinetic and pharmacodynamic (PK/PD) research and field investigations will be available for most zoo and wildlife animals, evidenced-based medicine will be caregivers translating available knowledge from similar species and combining that with their shared experiences. While this is not ideal, this is a common theme in veterinary medicine. For example, in small animal surgery a new treatment may become available. No published data exists, there is no oversight of the implants used; there is only how it might work because of how it worked in people and shared opinion. When faced with this situation I take the conservative path. The potential benefits must heavily outweigh the potential risks and the investment from the owner must not be greater than an available treatment that has greater evidentiary value.
For species where an untested drug for analgesic purposes is proposed, one can translate some evidence better than others. Sodium potassium channels work similarly in nearly all species. Bupivacaine blocks the influx of sodium into nerve cells and prevents depolarization. I think this is an example of a drug where the outcome of treatment can be accurately predicted. Oral tramadol has been shown to have wildly variable metabolism in different mammals. This is a drug where the outcome of treatment can be accurately predicted as wildly variable.
Developing and sharing a clinical opinion about the safety and efficacy of an analgesic must be done with caution. Some perspective on the accuracy of our opinions in this area can be gained from a review of the caregiver placebo effect. The caregiver placebo effect is a bit different to the widely accepted placebo effect. This is because when a placebo effect occurs the patient actually feels better. When a caregiver placebo effect occurs, the patient feels nothing (they may not even know they have received a treatment) but the caregiver feels the patient is better. This is an enormous source of bias when a caregiver measures outcome, and it has been consistently demonstrated in human medicine when parents assess the effect of medication on their children. More recently in a study of dogs that had lameness secondary to osteoarthritis, the caregiver placebo effect for pet owners and veterinarians was measured. The result, not surprisingly, was similar to findings of caregivers of human patients. Pet owners had a caregiver placebo effect of nearly 60% and veterinarians (veterinary surgeons) of 50%. From this study this means that the patient was treated with a placebo for its lameness and did not improve (limb function measured by computational gait analysis in an FDA-GCP study) but the caregiver thought it was better. The effect was also shown when the patient actually worsened but the caregiver thought the patient was better or unchanged. There are many reasons why a caregiver placebo effect occurs; we want our patients to improve and believe that our treatments should work. This data convinced me that when treating an individual patient, I must accept that any change I think I see could be from just my belief or from chance. The caregiver placebo effect can be overcome within an individual patient and within zoo and wildlife medicine. Implementing a single-case design study can do this. I think this would be especially helpful if treating a patient for a long-term condition. It works by choosing an outcome measure(s) and documenting that outcome for a period of time (e.g., two weeks). Then the intervention (e.g., medication) is given for the same period of time and the outcome is measured. This is then repeated for another cycle. After eight weeks the data can be reviewed, and one can scientifically evaluate how the intervention affected an individual patient.
1. Conzemius MG, Evans RB. Caregiver placebo effect in dogs with osteoarthritis. JAVMA. Accepted for publication, June 2011.
2. Evans RB, Conzemius MG, Robinson DA, McClure SR, Dahlberg JA, Brown TD. Single case designs in veterinary research. Am J Vet Res. 2006;67(1):189–195.