Plastic and Reconstructive Surgery • November 2013 timing of the patient’s own initial surgical intervention. While controlling for injury severity and other risk factors, patients treated at the worst-performing hospitals with delayed initiation of surgical intervention had an estimated 11 percent longer stay and 12 percent higher cost compared with patients at the best performing hospitals. It is important not only to evaluate the impact of individual variation on patient outcomes but also to examine system practices for quality improvement. Our study sought to better understand the impact that hospital-level delays may have on individual resource use. With a better understanding of practices at the hospital level, we may initiate a better evaluation of potential inefficiencies at the systems level rather than merely attributing all outcome differences to individual practice variation. DOI: 10.1097/PRS.0b013e3182a4c523

Erika Davis Sears, M.D., M.S. Section of Plastic Surgery Department of Surgery University of Michigan Health System, and Veterans Administration Health System Ann Arbor, Mich.

Kevin C. Chung, M.D., M.S. Section of Plastic Surgery Department of Surgery University of Michigan Health System Ann Arbor, Mich. Correspondence to Dr. Sears Section of Plastic Surgery University of Michigan Health System 1500 East Medical Center Drive 2130 Taubman Center SPC 5340 Ann Arbor, Mich. 48109-5340 [email protected]

DISCLOSURE The authors have no conflicts of interest to declare. REFERENCES 1. Sears ED, Burke JF, Davis MM, Chung KC. The influence of procedure delay on resource use: A national study of patients with open tibial fracture. Plast Reconstr Surg. 2013;131:553–563. 2. Godina M. Early microsurgical reconstruction of complex trauma of the extremities. Plast Reconstr Surg. 1986;78:285–292.

Herbal Products That May Contribute to Hypertension Sir: he article “Herbal Products That May Contribute to Hypertension” by Jalili et al. 1 contains several questionable statements and conclusions. Under the section “Bitter orange (Citrus aurantium),” the authors state that

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bitter orange contains two adrenergic agents, synephrine and octopamine, and that bitter orange increases blood pressure when it is combined with caffeine and also increases systolic and diastolic blood pressure. This statement is clearly inconsistent with the current research literature regarding bitter orange and p-synephrine.2–4 Octopamine is absent in bitter orange extract or present in inconsequential trace amounts, whereas p-synephrine comprises 90 percent or more of the total protoalkaloids.2 Furthermore, p-synephrine poorly binds to cardioresponsive α, β1, and β2 adrenoreceptors as compared with ephedra and phenylephrine.3 As a consequence, increases in heart rate and blood pressure are not expected at common doses. The results of more than 20 human studies involving bitter orange–containing products have recently been reviewed.4 Five published and two unpublished studies reported no cardiovascular effects when consuming products that contained only bitter orange. Five published and five unpublished studies using p-synephrine with other ingredients reported no cardiovascular effects (total of 170 subjects). As noted by the authors,1 small cardiovascular effects have been reported for a study that involved a total of 20 subjects consuming p-synephrine alone or with caffeine.4 The results of this study have been questioned due to experimental design.4 At a dose of 46.9  mg, p-synephrine had no effect on blood pressure, but when p-synephrine was used in combination with 239  mg caffeine, an increase in systolic and diastolic blood pressures were observed that the authors attributed to the caffeine and not p-synephrine.1 An increase in heart rate 6 hours after p-synephrine but not before does not coincide with the pharmacokinetics of the p-synephrine (2- to 3-hour half-life), but can be related to the consumption of a meal 3 hours after administration of the p-synephrine.2,4 A more recent study reported that the administration of p-synephrine at a dose of approximately 49 mg twice a day (total of 98 mg per day) to healthy human subjects for 60 days did not result in any significant changes in systolic or diastolic blood pressures, heart rate, blood chemistries, or hematologic studies.5 The authors referred to an early Health Canada report regarding bitter orange,1 but they failed to mention a much more recent report by the Natural Health Products Directorate of Health Canada involving an extensive review of bitter orange and p-synephrine.6 The report released in May of 2011 is a 49-page health risk assessment of p-synephrine, p-octopamine, and caffeine that redefines the previous guidelines for the use of these three natural ingredients. This is the latest and most definitive statement on the subject by Health Canada, and previous statements should be discounted. Health Canada has approved the use of up to 50 mg per day of p-synephrine alone in healthy adults, and 40  mg per day or less of p-synephrine when it is combined with 320  mg per day or less of caffeine. These doses are higher than the amount of p-synephrine in most available products. According to

Volume 132, Number 5 • Letters the Health Canada Report, under these conditions, p-synephrine “is not likely to cause any adverse health consequences.”6 Health Canada is the equivalent of the U.S. Food and Drug Administration. Intertek Cantox, a global leader in scientific, toxicology, and regulatory services, conducted an in-depth literature review of bitter orange/p-synephrine and issued a report in September of 2012 that redefines its guidelines for their use.7 The report notes that “p-synephrine is unlikely to have significant effects on inotropy, vasoconstriction, or blood pressure.” The report further states that the following dosages are “not likely to cause adverse effects”: up to 60 mg of p-synephrine alone or 40  mg in combination with 320  mg of caffeine; and if taken as divided doses spaced over the course of the day, 70  mg of p-synephrine alone or 60 mg of p-synephrine in combination with 320 mg of caffeine.7 It should also be noted that various orange juices contain up to 25 to 40 mg of p-synephrine per 8-ounce glass.8 Millions of individuals unknowingly consume p-synephrine daily in juices and orange food products as marmalades and do so without adverse events. Furthermore, tens of millions of doses of bitter orange products have been consumed by millions of individuals without report of serious incidents.2 Finally, contrary to widely held beliefs, no serious adverse cardiovascular effects have ever been directly attributable to bitter orange extract or p-synephrine,2,4 although the possibility exists that someone may experience hypertension in response to p-synephrine. In summary, the assertions that bitter orange and p-synephrine cause hypertension and present serious health concerns are not supported by the current research data. DOI: 10.1097/PRS.0b013e3182a4c4a6

Sidney J. Stohs, Ph.D., F.A.C.N., C.N.S., A.T.S. 7068 Maumee Valley Court Frisco, Texas 75034 [email protected]

DISCLOSURE The author has served as a consultant for Nutratech, Inc. (West Caldwell, N.J.), a company that markets bitter orange (Citrus aurantium) extracts. The author has no financial interest in any of the products, devices, or drugs mentioned in this communication. REFERENCES 1. Jalili J, Askeroglu U, Alleyne B, Guyuron B. Herbal products that may contribute to hypertension. Plast Reconstr Surg. 2013;131:168–173. 2. Stohs SJ, Preuss HG, Shara M. The safety of Citrus aurantium (bitter orange) and its primary protoalkaloid p-synephrine. Phytother Res. 2011;25:1421–1428. 3. Stohs SJ, Preuss HG, Shara M. A review of the receptor-binding properties of p-synephrine as related to its pharmacological effects. Oxid Med Cell Longev. 2011;2011:482973. 4. Stohs SJ, Preuss HG, Shara M. A review of the human clinical studies involving Citrus aurantium (bitter orange) extract

and its primary protoalkaloid p-synephrine. Int J Med Sci. 2012;9:527–538. 5. Kaats GR, Miller H, Preuss HG, Stohs SJ. A 60-day double-blind, placebo-controlled safety study involving Citrus aurantium (bitter orange) extract. Food Chem Toxicol. 2013;55:358–362. 6. Marles R. Synephrine, Octopamine and Caffeine Health Risk Assessment (HRA) Report. Health Canada Natural Health Products Directorate, File No. 172091, May 2011, pp.1–49. Available at: http://www.nutratechinc.com/advz/ advz.php?p=2. 7. Lynch B. Review of the safety data available on p-synephrine, caffeine and p-synephrine-caffeine containing combination products. Intertek-Cantox Report 2012;September 13:1–20. Available at: https://www.dropbox.com/s/xipg4dqz9f2p05w/ Intertek%20Cantox%20-%20Sep12.pdf. 8. Uckoo RM, Jayaprakasha GK, Nelson SD, Patil BS. Rapid simultaneous determination of amines and organic acids in citrus using high-performance liquid chromatography. Talanta 2011;83:948–954.

Importance of the Chin in Lower Facial Contour: Narrowing Genioplasty to Achieve a Feminine and Slim Lower Face Sir: t has been just 10 years since Park and Noh started “narrowing genioplasty” (Plast Reconstr Surg. 2008;122:261–268).1 In this article, the authors performed 39 cases of “central strip resection” to make the lower face slender and appear more feminine in contour. In this “mid-symphyseal sectioning procedure,” after the osteotomy was completed, the muscular attachment was stripped off and the central segment was removed. Since this procedure seemed to be very interesting and useful, many plastic surgeons have adapted and applied it in Korea. The authors stated that “complications included minor step-off at the chin-mandible junction, mild transient numbness of the lower lip, and bunching of the chin. Bony step-offs can be a potential challenge. We had few complaints from the patients in the first few cases, but as our surgical skill improved, step-offs were not a big problem.” Park and Noh removed the central portion of the chin, which ranged from 6 to 12  mm, including the mental spines (genial tubercle) and where the genioglossus muscle arises.2 In an earlier article that Park and Noh did not cite, Silverstein et al.3 dissected 10 adult cadavers and found that the average distance from the genial tubercle to the inferior border was 14.2  mm and the width of the genioglossus muscle itself was 13.8 mm3. Genioglossus brings about the forward traction of the tongue to protrude its apex from the mouth. Acting bilaterally, the two muscles depress the central part of the tongue, making it concave from side to side. Acting unilaterally, the tongue diverges to the opposite side.2 I would really like to know whether there were any limitations of tongue movement following

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Herbal products that may contribute to hypertension.

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