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The Impact of Herbal Medicines on Dermatologic Surgery Lawrence K. Chang, MD and Duane C. Whitaker, MD Department of Dermatology, University of Iowa College of Medicine, Iowa City, Iowa background. In recent years herbal medicines and supplements have become increasingly popular. With their increased popularity, more publications are warning about the potential harmful effects of some of these products. objective. To present scientific evidence of the benefits and surgical risks of herbal products. methods. A Medline search and review of the literature was performed. results. Many herbal medicines are relevant in dermatologic surgery since Ginkgo biloba, garlic, ginger, ginseng, feverfew, and vitamin E may increase the risk of bleeding, and ephedra may potentiate the side effects of epinephrine. conclusion. Dermatologists should be aware of these herbal products and their uses. Many of these products prescribed by alternative medicine physicians or purchased over the counter should be discontinued prior to dermatologic surgery to minimize the risk of surgical complications. ALTERNATIVE MEDICINE is becoming more popular in the United States. In 1997 alternative medicine practitioners had 629 million visits, exceeding total primary care physician visits. In addition, approximately $5.1 billion was spent on herbal preparations. The use of these products increased by 380% between 1990 and 1997, and appears to be growing by 15% per year.1,2 Since herbal product use has become more prevalent in recent years, more medical publications have reported their potential uses, side effects, and drug interactions, increasing awareness among physicians.3– 6 Furthermore, the general public is now more aware of the potential benefits and side effects. For example, the cover of the February 12, 2001 issue of U.S. News & World Report, titled “The Risks of Natural Cures,” is accompanied by an article addressing the potential benefits, side effects, and drug interactions of some popular herbal medicines and supplements. Many herbal products have antiplatelet effects, therefore they may increase the bleeding risk in dermatologic surgery. Postoperative bleeding subsequently increases the risk of infection, flap and graft necrosis, wound dehiscence, pain, and scar formation. Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) are known to inhibit platelet function and increase these risks. In order to minimize bleeding complications, aspirin is routinely stopped 10 days prior to surgery in patients without a prior history of a cardiovascular event, and NSAIDs are stopped 3 days prior to surgery to minimize bleeding complications. Table 1 lists the medications that contain aspirin and NSAIDs. In addition to aspirin, NSAIDs, and other physician prescribed antiplatelet drugs, herbal products such as Ginkgo biloba, garlic, ginger, ginseng, feverfew, and vitamin E due to their antiplatelet effects should be discontinued preoperatively if absolute hemostasis is critical. During the preoperative evaluation, patients sometimes mention that they are on herbal medicines. However, less than 40% of people actually disclose alternative medicine use with their physicians.1 Therefore the practitioner should ask the patient about use of specific herbal products which are known to inhibit platelet function. Fifty-eight percent of patients who take herbal medicines are using alternative medicine for prevention and maintaining health. Conversely, only 42% of people were using alternative medicine for treatment of an illness.1 Furthermore, half of the people use alternative medicine without a recommendation from a physician or a provider of alternative therapy.7 Thus many herbal products can be stopped prior to surgery. An understanding of the indications as well as the scientific data regarding the antiplatelet effects of herbal products is helpful to the physician during the preoperative evaluation. There is scientific evidence that Ginkgo biloba, ginger, garlic, ginseng, feverfew, and vitamin E inhibit platelet function and aggregation, and increase the risk of bleeding. A review of current literature on basic science research as well as clinical reports of bleeding on these herbal products are summarized. L. K. Chang, MD and D. C. Whitaker, MD have indicated no significant interest with commercial supporters. Address correspondence and reprint requests to: Duane C. Whitaker, MD, Department of Dermatology, University of Iowa Hospital and Clinics, Iowa City, IA 52242-1090. Ginkgo biloba Extracts for medicinal use are made from the dried leaves of Ginkgo biloba (maidenhair tree). In Ger- © 2001 by the American Society for Dermatologic Surgery, Inc. • Published by Blackwell Science, Inc. ISSN: 1076-0512/01/$15.00/0 • Dermatol Surg 2001;27:759–763 760 chang and whitaker: herbal medicine in dermatologic surgery Dermatol Surg 27:8:August 2001 Table 1. Aspirin-Containing Products Over-the-counter medications Prescription medications Alka-Seltzer Aspirin Aspirin Regimen Bayer BC powders Ecotrin Excedrin Extra Strength Goody’s Body Pain Formula powder Goody’s Extra Strength Pain Relief Momentum Backache Relief Vanquish Analgesic Caplets Easprin Excedrin Disalcid Salflex Trilisate NSAIDs Advil Aleve Motrin Nuprin Orudis KT Anaprox Arthrotec Cataflam Clinoril Daypro Disalcid Dolobid EC-Naproxyn Feldene Indocin Lodine Nalfon Naproxyn Oruvail Ponstel Kapseals Relafen Salflex Tolectin Toradol Trilisate Voltaren Celebrex and Vioxx are left out because they do not increase bleeding risk. Sources: Physicians’ Desk Reference, 54th edition, 2000. Physicians’ Desk Reference, for nonprescription drugs and dietary supplements, 21st edition, 2000. many and France, these extracts are the most commonly prescribed herbal drug.8 Ginkgo biloba has become a subject published extensively in the medical literature. A meta-analysis by Oken et al. of 57 articles concluded that Ginkgo biloba has shown some evidence of beneficial effect on memory function.9 In most studies 120–160 mg of Ginkgo biloba were used and divided into three times a day dosing. The beneficial effect usually starts around 4–6 weeks. Flavonoids and terpenoids are the main components of ginkgo extracts, which are potent antagonists of platelet-activating factor.10 Platelet-activating factor induces platelet aggregation and activation. The antiplatelet property of Ginkgo biloba may be clinically significant. Currently there are four reports of bleeding in association with Ginkgo biloba. In one case report, a healthy 33-year-old woman developed spontaneous subdural hematomas after 2 years of taking 120 mg/day of Ginkgo biloba. The patient’s bleeding time was prolonged while taking Ginkgo biloba and subsequently normalized when checked at 35 days after discontinuing Ginkgo biloba.11 In another case report, a 72-yearold woman who had been taking Ginkgo biloba for 6 months developed a subdural hematoma. Furthermore, the combination of Ginkgo biloba with other anticoagulants may increase the risk of hemorrhage. In one case report, a 78-year-old who was on chronic warfarin developed intracerebral hemorrhage with con- comitant use of Ginkgo biloba.12 In another case report, a 70-year old who was on 325 mg of aspirin for 3 years developed bleeding from the iris into the anterior chamber 1 week after starting Ginkgo biloba.13 Since people are taking Ginkgo biloba to increase memory function, a noncritical indication, and Ginkgo biloba has been reported to increase bleeding time and bleeding, Ginkgo biloba should be stopped prior to surgery. Garlic Garlic (Allium sativum) most recently has been used to lower cholesterol and blood pressure.14 Many studies have been published to show the beneficial effects of garlic. A meta-analysis done by Silagy and Neil15 showed that 600–900 mg/day of garlic may lower blood pressure over 1–3 months and lowers cholesterol by 10%. Adenosine, allicin, and paraffinic polysulfides are constituents of garlic that have antiplatelet effects. The antiplatelet effects of adenosine last up to 1 day, and allicin and paraffinic polysulfides have a much shorter time of action.16 In one study, 20 days of garlic oil decreased platelet aggregation by 9%.17 In a double-blind, placebo-controlled study, 800 mg/day of garlic produced a continuous decline of platelet aggregation for 4 weeks. Furthermore, during the wash- Dermatol Surg 27:8:August 2001 chang and whitaker: herbal medicine in dermatologic surgery out period, the platelet aggregation did not return to normal for 4 weeks.18 Three cases of bleeding have been reported with garlic. In one case report, a healthy 87-year-old man (not on anticoagulants) who ingested four cloves of garlic per day presented with a spontaneous epidural hematoma. His bleeding time and prothrombin time (PTT) were significantly elevated at admission. Three days after stopping the garlic, his bleeding time returned to normal.19 In another case report, a 72-year-old man on garlic supplement who underwent a transurethral prostatectomy had excessive bleeding and required a blood transfusion. Three months after resuming garlic tablets, platelet aggregation in the presence of collagen was abnormal.20 Burnham21 reported a patient on heavy dietary intake of garlic who had an abnormal bleeding time at the time of surgery. One week after the patient discontinued garlic, bleeding time normalized.21,22 Garlic supplement may be indicated in patients with hypertension or hypercholesterolemia, and garlic ingested in large amounts appears to have antiplatelet effects and should be stopped prior to surgery. Ginger Ginger (Zingiber officinale) has been used as an antinauseant and antispasmodic agent. In a prospective, randomized, double-blind trial, 1 g of ginger 1 hour prior to surgery reduced postoperative nausea by 50%. In this study, no increase in bleeding was noted during the postoperative period.23 In another study, coagulation studies were not affected 24 hours after ingesting 2 g of dried ginger. Therefore ginger should be safe as a preoperative antiemetic with doses of up to 2 g of dried ginger.24 Although short-term and relatively small doses of ginger appear to have no effect on coagulation studies, it does have an anticoagulant effect with larger doses or with chronic use. Ginger inhibits thromboxane A2 synthesis and promotes prostacyclin synthesis. Thromboxane A2 has a positive aggregatory effect on platelets, while, prostacyclin has a negative aggregatory effect.25 Therefore ginger inhibits platelet aggregation. In a prospective human trial, consumption of 5 g of raw ginger for 7 days showed a statistically significant reduction in thromboxane production.26 Small doses of ginger can be used as an antinauseant prior to surgery; however, large amounts of ginger may increase bleeding risk since ginger has an antiplatelet effect. 761 laboratory, ginseng extracts have been shown to have inhibitory effects on platelet aggregation and enhance fibrinolysis.32 Ginseng has also been reported to raise blood pressure; therefore it may increase bleeding risk.33 There are two reports of bleeding with ginseng use. The first report involved a 72-year-old postmenopausal woman who developed vaginal bleeding after ingestion of 200 mg of ginseng for 1 month.34 The second report involved a 44-year-old postmenopausal woman who had vaginal bleeding with the use of ginseng face cream.35 Since ginseng has the potential to increase blood pressure and has been reported to cause abnormal vaginal bleeding, ginseng is best stopped prior to surgery. Feverfew Feverfew is used for migraine headaches and arthritis. A double-blind, placebo-controlled trial has shown that feverfew prevents migraine attacks.36 Feverfew contains sesquiterpene lactone, which exerts its anti-inflammatory effect by inhibiting phospholipase breakdown of arachidonic acid into prostaglandins and leukotrienes.37,38 Thromboxane A2 is also a by-product of the cascade and induces platelet aggregation. Furthermore, the feverfew extract parthenolide inhibits platelet aggregation induced by phorbol 12-myristate 13-acetate, adenosine diphosphate, and sodium arachidonate.39,40 Feverfew has antiplatelet effects; however, the clinical significance of the inhibition of platelet aggregation is unknown. Vitamin E Vitamin E has antioxidant effects, which have been advocated for cancer prevention and reduction of oxidative damage of the central nervous system. Furthermore, vitamin E inhibits platelet aggregation and secretion.41 Therefore vitamin E has also been advocated in cardiovascular disease prevention. However, a recent study has shown that vitamin E does not reduce cardiovascular outcome in high-risk patients.42 Clinically vitamin E may cause bleeding. In one study, a 50 mg vitamin E supplement increased hemorrhagic stroke by 50% compared to a control group.43 In another related study, vitamin E has been associated with increased gingival bleeding.44 Vitamin E use in premature infants causes retinal hemorrhage.45 Since vitamin E has antiplatelet effects, vitamin E should be stopped prior to surgery. Ginseng Ginseng has been used to treat diabetes and to improve subjective well-being. In laboratory rats, ginseng extracts have a hypoglycemic effect.27–31 In the Ephedra Ephedra is commonly used as a weight loss product. Reported adverse reactions are insomnia, nervousness, 762 chang and whitaker: herbal medicine in dermatologic surgery tremor, headache, hypertension, seizure, arrhythmia, heart attack, stroke, and death. Half of the reported cases occurred in people younger than 40 years old.6 The potential interaction with epinephrine is of concern. In dermatologic surgery, epinephrine is often combined with lidocaine to decrease bleeding during surgery. The patient may feel palpitations when epinephrine is used. Since both epinephrine and ephedra can add to cardiac stress during surgery, ephedra is best avoided prior to dermatologic surgery. Conclusion Herbal medicines are gaining in popularity and are here to stay. Physicians need to heighten their awareness of herbal products. If physicians notice a complication related to herbal medicines, a report should be made to the U.S. Food and Drug Administration. The decision to discontinue or initiate a medicine prior to surgery should be made based on the overall wellbeing of the patient. However, the information provided herein about herbal medicines indicates that in dermatologic surgery, Ginkgo biloba, ginger, garlic, ginseng, feverfew, and vitamin E should be stopped prior to surgery to minimize bleeding risk, while ephedra-containing products should be discontinued to avoid potentiation of epinephrine. Acknowledgment We would especially like to thank Donna M. Pellowski, MD for assistance in reviewing and editing this article. References 1. Eisenberg DM, Davis RB, Ettner SL, Appel S, Wilkey S. Trends in alternative medicine use in the United States, 1990–1997. JAMA 1998;280:1569–75. 2. Marwick C. Growing use of medicinal botanicals forces assessment by drug regulators. JAMA 1995;273:607–9. 3. Miller LG. Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med 1998;158:2200–211. 4. Smolinske SC. Dietary supplement-drug interactions. J Am Med Womens Assoc 1999;54:191–2. 5. Fugh-Berman A. 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