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Dear Editor,

After reading the article entitled “Pain Induced by a Minor Medical Procedure (Bone Marrow Aspiration) in Dogs: Comparison of Pain Scales in a Pilot Study” by M. Guillot et al,[1] I believe that the authors are making conclusions that cannot be made from the study as presented due to inappropriate statistical analysis and study design.

Even with various forms of local anesthesia and analgesic premedications, bone marrow aspiration (BMA) is associated with pain in the majority of people who undergo the procedure,[2] some of whom even label it as “unbearable.”[3] According to the position statement issued by the American Academy of Pediatrics, “For procedural pain that is predictably severe and for which local measures give inadequate relief, such as for bone marrow aspirations, the use of systemic agents is required to bring pain to acceptable levels.”[4] Because of the acute pain caused by BMA, the procedure is most often performed under general anesthesia or heavy sedation in children. Aside from the lack of sedation or anesthesia provided to these 8 research animals, even the authors’ choice of pre-emptive analgesia with deracoxib (1mg/kg PO, 2 hours prior to BMA) might be considered inappropriate. Deracoxib is a COX-2 selective NSAID that is indicated for osteoarthritis and postoperative orthopedic pain due to inflammation.[5] However, BMAs are thought to cause minimal inflammatory pain; instead, the pain reported by humans is characterized as sharp, intense and piercing. In addition, according to the manufacturer's label, the bioavailability of Deracoxib is significantly reduced unless given with food, which was not done in this study.[6] Although some of the dogs in the study received lidocaine to anesthetize the skin and subcutaneous tissue, a needle piercing skin and soft tissue is not considered to be as painful as a needle piercing periosteum and bone. Furthermore, humans report significant “sucking” pain during aspiration,[7] which is not prevented by a subcutaneous lidocaine block or oral NSAID administration.

It is also of concern that the authors do not describe implementation of rescue analgesia, as the pain scores indicate it was necessary in some of the animals. Additionally, the methods of restraint used in unsedated animals was not described and it is not out of the realm of possibility that unsedated and restrained animals were demonstrating signs of fear that masked evaluated signs indicating pain.

With respect to statistics, the first problem is that the authors state, “Agreement between SF-Glasgow and 4A-VET and the progression of pain scores were analyzed using the mixed model method for Poisson-distributed repeated measures.” However, the authors did not test the data to determine if it was Poisson. In fact, with an n = 4 in 2 groups and an n = 8 in the other group, there is no way to test if the data are in fact Poisson. Second, this study uses several repeated measures and multiple levels of nesting by evaluating each dog at different times using two different observers. In short, there is an absence of independence between the various levels that was not appropriately accounted for. Thus, it is inappropriate for the authors to say, “pain scores are the median of both observer scores,” because this is akin to comparing apples to oranges. The interobserver correlation indicated that the expert observer was consistent with the use of IAI and NBI scoring systems, suggesting that the other observer required additional training. Thus, if the ratings differ between observers, the clinical outcome is also likely to be different.

Third, the authors extensively discuss the difference between observers in the discussion. They state, “However, lower interobserver correlations between the 4A-VET scale and IAI may be explained by either a skewed distribution of the data or possible interobserver variability for each item on the scale.” In short, this statement indicates that one explanation for the difference is that the data are not Poisson. For a Poisson distribution, the mean (λ) equals the variance (λ).

In summary, the conclusions made by the authors cannot be considered valid based on the statistical analysis presented.

References

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  2. References
  • 1
    Guillot M, Rialland P, Nadeau ME, et al. Pain induced by a minor medical procedure (bone marrow aspiration) in dogs: Comparison of pain scales in a pilot study. J Vet Intern Med 2011;25:10501056.
  • 2
    Vanhelleputte P, Kristel N, Delforge M, et al. Pain during bone marrow aspiration: Prevalence and prevention. J Pain Symptom Manage 2003;26:860866.
  • 3
    Degen C, Christen S, Rovo A, et al. Bone marrow examination: A prospective survey on factors associated with pain. Ann Hematol 2010;89:619624.
  • 4
    American Academy of Pediatrics. Policy Statement: The Assessment and Management of Acute Pain in Infants, Children and Adolescents. Pediatrics 2001;108:793797.
  • 5
    Curry S, Cogar S, Cook J. Nonsteroidal antiinflammatory drugs: A review. JAAHA 2005;41:298309.
  • 6
    Novartis Animal Health. Deracoxib package insert. 2008.
  • 7
    Shabanloei R, Golchin M, Esfahani A, et al. Effects of music therapy on pain and anxiety in patients undergoing bone marrow biopsy and aspiration. AORN J 2010;91(6):74651.