Letters to the Editor

Thrombophlebitis: A Common Complication of Amiodarone

to the editor: I read with interest the excellent article1 by Dr. Siddoway on the clinical use of the antiarrhythmic drug amiodarone (Cordarone) that appeared in the December 1, 2003, issue of American Family Physician. The author clearly presented the effectiveness and adverse effects related to this therapy that has been used intravenously or orally to convert and prevent recurrences of cardiac arrhythmias. However, there was no mention in the article1 of thrombophlebitis, a common complication associated with intravenous amiodarone.2

Recent studies3 have reported rates of phlebitis as high as 16 percent with the intravenous administration of amiodarone. A meta-analysis4 of 18 randomized controlled trials studying intravenous amiodarone to convert atrial fibrillation reported an 8 percent rate of phlebitis among the 550 patients who received amiodarone. In this systematic review,4 phlebitis was the most common adverse effect of the drug, followed by bradycardia (4 percent of patients) and hypotension (2 percent of patients).

Thrombophlebitis usually occurs when high doses of amiodarone are infused over a long period in peripheral veins. Thus, to avoid this side effect, the drug should be administered in a peripheral vein for a maximum of 24 hours. Afterwards, the drug must be used orally or a central vein access should be considered.5 By following these precautions, this minor but frequent complication can be avoided.

HENRIQUE HORTA VELOSO, M.D.
ANGELO AMATO VINCENZO DE PAOLA, M.D.
VOTCOR-Hospital da Venerável Ordem Terceira da Penitência
Rua Conde de Bonfim 1033, Tijuca
Rio de Janeiro, Brazil 20530-001

REFERENCES

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Definitive Statements Should Only Be Made with Evidence

to the editor: I found the final comments of the article "Black Cohosh,"1 to be paradoxical and not what I would expect to be accepted by any medical journal. The authors states: "Although the clinical trials on black cohosh are of insufficient quality to support definitive statements, this herbal medicine does appear to be effective in the short-term treatment of menopausal symptoms."1 One has to question how he can make this statement with authority if there are no studies that support this conclusion. The author admits that the studies2 he cites from Germany are based on case reports and are not randomized controlled studies. Therefore, he provides no definitive proof that black cohosh alleviates menopausal symptoms.

I believe this is another unfortunate example of giving various herbal or over-the-counter products more slack in their scientific study. If this had been a large, controlled study of a medication for heart disease that found no evidence of efficacy, we would not make assumptions that it is effective in the short-term treatment of symptoms. The author's conclusion that black cohosh appears effective in the short-term treatment of menopausal symptoms is just biased speculation and not a scientific conclusion.

I fear that physicians and researchers are drifting backward into testimonials to make their clinical decisions. I think we have to hold natural products to the same standards that we hold every other agent, and we should not let statements like this one go unchallenged. The problem with such statements is that they are repeated by those who wish to promote these products. If a journal such as American Family Physician prints a statement like this in a reviewed article, it suggests that the journal is in agreement with these conclusions. I think this is sloppy science and sloppy medicine.

BRUCE BONDE, M.D.

Allina Medical Clinic
8675 Valley Creek Rd.
Woodbury, MN 55125

REFERENCES

1. Kligler B. Black cohosh. Am Fam Physician 2003;68:114-6.

2. Blumenthal M. German Federal Institute for Drugs and Medical Devices. Commission E. The Complete German Commission E monographs: therapeutic guide to herbal medicines. Austin, Tex.: American Botanical Council, 1998.

in reply: Dr. Bonde makes an important point regarding the difficulty of making clinical decisions regarding herbal products given the frequent lack of definitive evidence from clinical trials. Although the conclusions in my review article on black cohosh1 were based on small clinical trials (not case reports, as Dr. Bonde states), the fact remains that more research on black cohosh is needed. Unfortunately, the large, randomized, double-blind controlled trials that are performed on new medications rarely are done for herbal products. This is partially because the financing for these trials, which often comes from pharmaceutical companies that are motivated by the profit potential of a new medication, is not available for the generally nonpatentable botanical products. Nevertheless, the evidence for the efficacy of black cohosh for menopausal symptoms was sufficient for the American College of Obstetricians and Gynecologists to recommend its use.2

An important question raised by Dr. Bonde is whether the standard of evidence of efficacy required should be uniform for all treatments, or whether this standard should be flexible depending on the safety margin of the treatment under discussion. Clearly, the standard of evidence of safety must be uniform. An herbal product known to have significant adverse effect potential should be used as cautiously as a medication or surgical procedure known to have such potential. But, when the safety margin is wide, as it clearly is with black cohosh, some would argue that we should tolerate a somewhat softer standard of evidence of efficacy in our clinical decision-making analysis of risk versus benefit.3 In fact, such a standard already is tolerated for many over-the-counter medications. For products with an adverse effect potential that is higher, the strictest standards of evidence of efficacy should be used. This is a challenging question in this age of evidence-based medicine, but it is a question worthy of discussion as we move forward in our understanding of how to incorporate the use of natural medicines into our work with patients.

BENJAMIN KLIGLER, M.D., M.P.H.
Beth Israel Center for Health and Healing
245 Fifth Ave.
New York, NY 10016

REFERENCES

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Suggestions for Performing Aspiration of Breast Cysts

to the editor: I enjoyed the article "Breast Cyst Aspiration,"1 in the November 15, 2003, issue of American Family Physician. As a diagnostic radiologist, I've aspirated thousands of breast cysts and would like to offer a few suggestions regarding the management of cysts.

I think the aspiration technique is even simpler than the authors1 indicate. By cleansing the skin that will be punctured by the needle with two or three alcohol wipes, povidone-iodine swabs or sterile drapes are not necessary.

There is fairly good evidence2-4 that injecting an equivalent volume of air into the cyst after aspirating the fluid prevents or markedly reduces the propensity for cyst fluid reaccumulation. Desiccation of the fluid-secreting cells that line the cyst interior has been proposed as the mechanism. The air injection is accomplished by unscrewing the syringe from the needle with the needle in situ, evacuating the aspirated cyst's fluid from the syringe into a container or test tube, drawing an equivalent volume of air back into the syringe, reattaching the syringe, and injecting the air. This takes
20 seconds and may prevent cyst recurrence. Patients will have a soft mushy mass where the cyst had been, and the air resorbs during the ensuing days. Before ultrasonography was generally available in breast-imaging facilities, we would perform "pneumocystogram" mammography after injecting the air to exclude the possibility of intracystic mass.

In my experience, thick gelatinous cyst fluid is simply "old" fluid with high protein content. Intracystic neoplasms are papillary cancers or papillomas, and do not have this type of intracystic fluid; it is generally new or old blood resulting from spontaneous hemorrhage or local needle trauma to the friable papillary fronds that occurs during the aspiration procedure. I've watched numerous colloid-filled cysts completely disappear with aspiration under real-time ultrasound observation. It is okay to simply discard viscous fluid from cysts if it is not bloody. Even in the case of documented intracystic papillary cancer, the sensitivity of cytologic diagnosis from the cyst fluid is quite poor. In general, cyst fluid cytology is seldom helpful, and may even force unnecessary surgical biopsies in cases where the cytology shows "atypia."

If no fluid is obtained during the first stick, I would urge physicians to stop and maintain firm pressure to minimize bruising, because hematomas can complicate breast imaging by obscuring true masses.

Lastly, the authors1 note that surgical referral is recommended for refilling of cysts or residual mass after aspiration. Actually, breast imaging is the most logical next step. A work-up would include a diagnostic mammogram following placement of a metallic marker over the palpable finding, and an ultrasound examination of the region using current-generation equipment. Only after a thorough imaging evaluation should the need for tissue sampling be addressed. The radiologist usually should decide whether or not tissue diagnosis is needed. If tissue sampling is needed, it could be done with core needle biopsy at the time of the diagnostic mammogram, and all data necessary for management would be obtained during one visit to the radiology department.

DAVID R. PENNES, M.D.
Betty Ford Diagnostic Breast Center
1840 Wealthy SE
Grand Rapids, MI 49506

REFERENCES

editor's note: This letter was sent to the authors of "Breast Cyst Aspiration," who de-clined to reply.

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NSAIDs Should Not Be Used in Treatment of Stress Fractures

to the editor: The article by Drs. Sanderlin and Raspa, "Common Stress Fractures,"1 reports, quite correctly, on the frequency and potential seriousness of stress fractures. We compliment American Family Physician for making it the cover article of the October 15, 2003, issue. However, we feel a need to comment on the author's recommendation of the use of nonsteroidal anti-inflammatory drugs (NSAIDs) as a treatment for stress fractures.

The article repeatedly lists NSAIDs as a recommended treatment for "all stress fractures." We are unaware of any data that suggest that NSAIDs are beneficial in the treatment of stress fractures. In fact, there is an increasing amount of literature suggesting that they may be harmful. A retrospective study of a cohort of more than 700,000 cases found that regular use of NSAIDs was associated with a 1.47 relative risk of nonvertebral fractures compared with control patients who did not receive NSAIDs.2 Another study compared 32 patients with nonunion of femoral fractures with 67 patients whose fractures had united. The results demonstrated a "marked association" between nonunion and the use of NSAIDs.3 These retrospective analyses are consistent with some prospective animal data demonstrating that NSAIDs retard fracture healing.4 Finally, it has been well established that NSAIDs inhibit heterotopic ossification (i.e., new bone formation) after total hip replacement and acetabular fractures.5

There is biologic plausibility for a detrimental effect of NSAIDs on bone healing. Inflammation is a necessary step in the healing of normal body tissues, and osteoblasts specifically require prostaglandins for osteogenesis and differentiation. By inhibiting these prostaglandins, NSAIDs may delay osteoblastic formation of new bone.

Additionally, NSAIDs have a strong analgesic effect. The article1 correctly encourages using the symptom of pain as a guide to increasing activity. A 10-year review6 of stress fractures in varsity athletes at the University of Minnesota validates this recommendation. While we want our patients to be pain free, masking the pain of stress fractures may compromise recovery. This is especially true of more dangerous stress fractures such as those of the femoral neck.

In our clinical practices we discourage the use of NSAIDs in patients with stress fractures. Based on our understanding of the physiology of bone healing and the clinical data available, we urge your readers to do the same.

STEVEN D. STOVITZ, M.D.
Team Physician, University of Minnesota Athletic Dept.
University of Minnesota
Dept. of Family Medicine and Community Health
2615 E. Franklin Ave.
Minneapolis, MN 55406

elizabeth a. arendt, m.d.
Medical Director, University of Minnesota Athletic Dept.
University of Minnesota
Dept. of Orthopaedic Surgery
2450 Riverside Ave.
Minneapolis, MN 55454

REFERENCES

editor's note: This letter was sent to the authors of "Common Stress Fractures," who declined to reply.

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Correction

The article "DVT and Pulmonary Embolism: Part 1. Diagnosis" (June 15, 2004, page 2829) contained an error in the Wells clinical prediction rule for pulmonary embolism. On page 2834, in Table 3, the third entry was incorrectly given as "Heart rate less than 100 beats per minute" when it should have stated "Heart rate greater than 100 beats per minute." The online version of this article has been corrected, and the corrected table is reprinted below.

TABLE 3 Wells Clinical Prediction Rule for PE Clinical feature Points Clinical symptoms of DVT 3 Other diagnosis less likely than PE 3 Heart rate greater than 100 beats per minute 1.5 Immobilization or surgery within past 4 weeks 1.5 Previous DVT or PE 1.5 Hemoptysis 1 Malignancy 1 Total points: PE = pulmonary embolism; DVT = deep venous thrombosis. Risk score interpretation (probability of DVT): >6 points: high risk (78.4%); 2 to 6 points: moderate risk (27.8%); <2 points: low risk (3.4%) Adapted with permission from Wells PS, Anderson DR, Rodger M, Ginsberg JS, Kearon C, Gent M, et al. Derivation of a simple clinical model to categorize patients' probability of pulmonary embolism: increasing the model utility with the SimpliRED d-dimer. Thromb Haemost 2000;83:418.

Send letters to Jay Siwek, M.D., Editor, American Family Physician, 11400 Tomahawk Creek Pkwy., Leawood, KS 66211-2672; fax: 913-906-6080; e-mail: afplet@aafp.org.

Please include your complete address, telephone number, fax number, and e-mail address. Letters should be submitted on disk, double-spaced, fewer than 500 words, and limited to one table or figure and six references. Please submit a word count.

Letters submitted for publication in AFP must not be submitted to any other publication. Possible conflicts of interest must be disclosed at time of submission. Submission of a letter will be construed as granting the AAFP permission to publish the letter in any of its publications in any form. The editors may edit letters to meet style and space requirements.

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