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Letters to the Editor to:

Scientific Articles:
Steven J. Morgan, Kyle J. Jeray, Laurel H. Saliman, Howard J. Miller, Allison E. Williams, Stephanie L. Tanner, Wade R. Smith, and J. Scott Broderick
Continuous Infusion of Local Anesthetic at Iliac Crest Bone-Graft Sites for Postoperative Pain Relief. A Randomized, Double-Blind Study
J Bone Joint Surg Am 2006; 88: 2606-2612 [Abstract] [Full text] [PDF]
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[Read Letter to the Editor] Dr. Jeray et al. respond to Dr. Blumenthal
Kyle J. Jeray, M.D., Allison E. Williams, Steven J. Morgan, Stephanie L. Tanner, Wade R. Smith, and J. Scott Broderick   (4 January 2007)
[Read Letter to the Editor] Continuous Infusion of Local Anesthetic at Iliac Crest Bone-Graft Sites
Stephan Blumenthal, M.D., Alain Borgeat, M.D.   (4 January 2007)

Dr. Jeray et al. respond to Dr. Blumenthal 4 January 2007
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Kyle J. Jeray, M.D.
Greenville Hospital System, Greenville, SC,
Allison E. Williams, Steven J. Morgan, Stephanie L. Tanner, Wade R. Smith, and J. Scott Broderick

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Re: Dr. Jeray et al. respond to Dr. Blumenthal

kjeray{at}ghs.org Kyle J. Jeray, M.D., et al.

We appreciate the interest by Dr. Blumenthal in our paper(1). The first issue raised regarding the concentration and volume differences may indeed aid in explaining the differences observed between the two studies, however we would also like to point out that several other differences also exist between the studies. We did not administer continuous analgesia at the second operative site nor did we bolus the iliac crest graft site with 30 cc of ropivicaine prior to beginning use of the pump. We agree that further studies are needed to clarify these issues.

The “methodological concerns” regarding the nonstatistical remarks were addressed in the body of the discussion and we would agree, as noted in the paper, the pain at the surgical recipient site may influence the results. I would refer Dr. Blumenthal to the last three paragraphs of the paper addressing this very concern.

Again, as noted in the discussion, study limitations include the variation in the graft harvest site, the degree and variation in recipient sites, and the size of the trap-door osteotomy. When analyzing these variables the analysis demonstrated no statistical differences.

Another interesting issue raised by Dr. Blumenthal was the effect of narcotics on activity-induced pain. We concede that opioids, contrary to local anesthetics, are weak blockers of the A-sigma fibers, which are closely linked to movement and by obtaining a pain score (via VAS) during motion one might have different results compared to at rest. However this is certainly not done in most studies. And even when done, as in his study, the pain scores, as expected, were unchanged or worse. So we feel that this would have had little impact on our study conclusions. However this may be an area that warrants additional studies in the future.

We also appreciate the statistical comments provided by Dr. Blumenthal. He correctly points out the possibility that the loss of two subjects in the study may have decreased our power thereby limiting the ability to detect the difference specified as clinically meaningful. An analysis of the effect size produced in this study, however, indicates that it is highly unlikely that the addition of two subjects would change the study results. Given the small difference found between groups in mean average donor site pain scores, a power calculation indicates that 4800 subjects would be required to detect this difference assuming alpha = 0.05 and power = 0.80. As described in the article, such a small difference was not considered clinically significant, and it is improbable that the addition of one subject to each group would have produced statistical significance. Regarding the repetitive pain assessment, Dr. Blumenthal also correctly notes the need for an adjustment to the alpha value due to multiple comparisons. This need was recognized by the authors, and identified as a limitation of the study in the discussion section in which it is stated that the statistically significant difference at the 24 hour time point was likely a chance finding resulting from multiple comparisons. It is notable that this is the only statistically significant finding reported across the time points, and that while the Bonferroni adjustment would have reduced the alpha level required for statistical significance it would not have changed the statistical test nor the overall conclusions of nonsignificance for the other time points.

Reference:

1. Morgan SJ, Jeray KJ, Saliman LH, Miller HJ, Williams AE, Tanner SL, Smith WR, Broderick JS. Continuous infusion of local anesthetic at iliac crest bone-graft sites for postoperative pain relief. 2006;88:2606-2612.
Continuous Infusion of Local Anesthetic at Iliac Crest Bone-Graft Sites 4 January 2007
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Stephan Blumenthal, M.D.,
Consultant
Department of Anesthesiology, Orthopedic University Clinic Balgrist, Zurich, Switzerland,
Alain Borgeat, M.D.

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Re: Continuous Infusion of Local Anesthetic at Iliac Crest Bone-Graft Sites

stephan.blumenthal{at}balgrist.ch Stephan Blumenthal, M.D., et al.

To The Editor:

We read with interest the article by Morgan SJ, et al. (1) demonstrating the ineffectiveness of continuous local anesthetic infusion to the iliac crest bone graft site. These results are surprising and not in accordance with the ones found in a quite similar, recent investigation (2). Several methodological concerns have to be discussed.

The analgesic regimen with continuous infusion of bupivacaine 0,5 % 2 ml/h might be insufficient because of a limited spread of this small volume. A continuous administration of ropivacaine 0,2 % with an infusion rate of 5ml/h over 48 hours was successfully used in this surgical context(2). The question of volume may be more important than the concentra-tion in this setting. This may explain the differences observed between the two studies, but further studies will be needed to clarify this issue.

The results of the study may be compromised by the influence of the pain from the surgical recipient site. This can influence the pain perception at the iliac bone graft site. This factor can also have been influenced by the heterogeneous surgical locations including various graft harvest and recipient sites. Additionally, the lack of a precise definition whether pain at rest or pain in motion has been assessed, is important when regarding the limited potency of narcotics to treat activity-induced pain (3,4).

The authors calculated that 60 patients would have been necessary to achieve power, so with 58 complete data sets, the study is underpowered.

Finally, regarding the repetitive pain assessment, the statistics used are not correct since no correction for repeated measurement has been made.

The authors did not receive any outside funding or grants in support of their research for or preparation of this work. Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.

References:

1. Morgan SJ, Jeray KJ, Saliman LH, Miller HJ, Williams AE, Tanner SL, Smith WR, Broderick JS: Continuous infusion of local anesthetic at iliac crest bone-graft sites for postoperative pain relief. A randomized, double-blind study. J Bone Joint Surg Am 2006; 88: 2606-12

2. Blumenthal S, Dullenkopf A, Rentsch K, Borgeat A: Continuous infusion of ropivacaine for pain relief after iliac crest bone grafting for shoulder surgery. Anesthesiol-ogy 2005; 102: 392-7

3. Gall O, Aubineau JV, Berniere J, Desjeux L, Murat I: Analgesic effect of low-dose intrathecal morphine after spinal fusion in children. Anesthesiology 2001; 94: 447-52

4. Pirec V, Laurito CE, Lu Y, Yeomans DC: The combined effects of N- type calcium channel blockers and morphine on A delta versus C fiber mediated nociception. Anesth Analg 2001; 92: 239-43