53: Herbal Supplements

Published on 27/02/2015 by admin

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CHAPTER 53 Herbal Supplements

James Duke, MD, MBA

1 How does the Federal Food and Drug Administration regulate herbal medications?

In 1994 the Food and Drug Administration (FDA) implemented the Dietary Supplement Health and Education Act, which outlines the regulation of botanicals, called dietary supplements. Under this act manufacturers of alternative medications operate under less rigid guidelines than prescription pharmaceutical companies. The lack of rigorous regulation has resulted in a lack of standardization of doses and purity, contamination with undeclared pharmaceuticals and heavy metals, failure to report adverse events, and no requirement to demonstrate safety or efficacy. However, when presented with a supplement with obvious toxicity issues such as the stimulant effects of ephedra, the FDA does intervene to limit its availability; ephedra is no longer available as an over-the-counter product.

2 What is the incidence of herbal medicine use in the surgical patient population? What are commonly used herbal medicines?

In 2001 over $4 billion was spent on herbs and other botanical remedies. Reported use varies widely, but a self-administered questionnaire of preoperative patients found an incidence of about 40%. Often these are taken without input from a physician. The number of individuals using herbal remedies is rising annually. Use in women is higher than in men, and patients with either neoplastic disease or human immunodeficiency virus have also been noted to use supplements with greater frequency. Supplements most commonly used include vitamins (especially vitamins E and C), garlic (Allium sativum), fish oil, ginkgo biloba (ginkgo), ginseng, Zingiber officinale (ginger), Hypericum perforatum (St. John’s wort), Echinacea angustifolia, valerian, 2-amino-2-deoxyglucose sulfate (glucosamine), chondroitin 4-sulfate, chamomile, kava, and Tanacetum parthenium (feverfew). Oriental patients who receive concoctions from Chinese herbalists often receive more potent compounds with many different herbs contained therein.

3 How can commonly used herbal medicines adversely affect the surgical patient?

Although these supplements are considered natural, they are not free of harmful side effects. They have central nervous and cardiovascular effects (e.g., ephedra) and interact with prescription drugs. For example, St. John’s wort induces the cytochrome P-450 enzymes, accelerating the breakdown of cyclosporine, antiretroviral drugs, digoxin, and warfarin, resulting in a fall in drug levels to subtherapeutic concentrations. Nephrotoxic, hepatotoxic, and carcinogenic effects have been associated with products containing kava, comfrey. Of greatest concern in the perioperative period are effects on coagulation. Vitamin E, garlic, fish oil, ginkgo, ginseng, ginger, and feverfew have anticoagulant potential.

4 What are the risks involved in consuming ephedra?

Ephedra alkaloids have been marketed as a way to boost energy and lose weight. These compounds are powerful cardiovascular and central nervous system stimulants, and severe hypertension, dysrhythmias, myocardial infarction, acute psychosis, seizures, cerebrovascular accidents, and death have been associated with their use. It may be particularly toxic when combined with caffeine. Many hundreds of people have been hospitalized after their use and, as mentioned previously, the FDA has prevented its over-the-counter availability.

5 Review the effects of vitamin E

Vitamin E is consumed for the prevention and treatment of cardiovascular disease, diabetes mellitus, and some forms of cancer. Vitamin E is an antioxidant that prevents the formation of free radicals, but high doses may increase bleeding caused by antagonism of vitamin K–dependent clotting factors and platelet aggregation. Concomitant use of vitamin E and anticoagulant or antiplatelet agents, including aspirin, clopidogrel (Plavix), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, ticlopidine (Ticlid), and warfarin (Coumadin) may potentiate the risk of bleeding.

6 What are the reported benefits and adverse effects of fish oil?

Fish oils are used primarily in the treatment of hyperlipidemia, hypertension, and chronic inflammatory states such as rheumatoid arthritis and autoimmune disease. Fish oils contain two long-chain omega-3 fatty acids that compete with arachidonic acid in the cyclooxygenase and lipoxygenase pathways and have antiinflammatory effects, likely caused by the inhibition of leukotriene synthesis. Fish oils decrease blood viscosity and increase red blood cell deformability. The antithrombotic activity of fish oils results from prostacyclin inhibition, vasodilation, reduction in platelet count and adhesiveness, and prolongation of bleeding time. Concomitant use of fish oils and anticoagulant and antiplatelet drugs previously mentioned may increase the risk of bleeding.

7 What are the beneficial properties and side effects of kava and valerian?

Kava is antiepileptic, anxiolytic, and sedative in its effects and may potentiate prescribed medications with similar properties. Its action is thought to be through stimulation of γ-aminobutyric (GABA) pathways. Valerian is also a sedative, potentiates the actions of barbiturates and other sedatives, and is probably GABA stimulating. These medications may potentiate the effects of anesthetic medications.

8 Review the alleged benefits and risks of ginkgo

Ginkgo is used for the treatment of dementia, Alzheimer’s disease, and conditions associated with cerebral vascular insufficiency, including memory loss, headache, tinnitus, vertigo, difficulty concentrating, mood disturbances, and hearing disorders. Active ingredients of ginkgo leaf and its extracts include flavonoids, terpenoids, and organic acids. Although the mechanism of action is only partially understood, there are several theories about how ginkgo works. Ginkgo may protect tissues from oxidative damage by preventing or reducing cell membrane lipid peroxidation and decreasing oxidative damage to erythrocytes, and it may protect neurons and retinal tissue from oxidative stress. Extracts from the ginkgo leaf competitively inhibit platelet-activating factor, decreasing platelet aggregation, phagocyte chemotaxis, smooth muscle contraction, and free radical production, and prevent neutrophil degranulation. A case of bilateral spontaneous subdural hematomas has been linked to chronic ginkgo ingestion. Use of ginkgo may potentiate anticoagulant or antiplatelet agents.

9 What are the alleged benefits and risks of ginseng?

Ginseng is a general tonic for improving well-being and stamina and may increase resistance to environmental stress. The active constituents of ginseng are ginsengosides; these compounds may raise blood pressure and act as a central nervous system stimulant. Adrenal function and cortisol release may increase. Ginsengosides are reported to interfere with platelet aggregation and coagulation in vitro, but this effect has not been demonstrated in humans. Ginseng is also associated with hypoglycemia, interferes with warfarin, and may increase partial thromboplastin time.

10 Review the alleged benefits and risks of garlic

Garlic decreases blood pressure and reduces plasma lipids. It may produce smooth muscle relaxation and vasodilation by activation of endothelium-derived relaxation factor. It has been shown to have antithrombotic properties by increasing thrombolytic activity secondary to plasminogen activation and decreasing platelet aggregation through inhibition of thromboxane B2 formation. Garlic may potentiate the effects of warfarin, heparin, nonsteroidal antiinflammatory drugs (NSAIDs), and aspirin. A spontaneous spinal epidural hematoma associated with excessive garlic ingestion has been reported. However, garlic taken in normal dietary doses does not impair platelet function.

11 What about ginger?

Ginger is used for the treatment of arthritis, for a variety of gastrointestinal complaints, for vertigo and motion sickness, and as an antiemetic. It is effective in controlling nausea and vomiting in hyperemesis gravidarum. Its active component is gingerol, and its mechanism of action is unclear, although gingerols are thought to inhibit prostaglandin and leukotriene synthesis. Ginger is believed to inhibit thromboxane synthetase, decreasing platelet aggregation. Like garlic, it may potentiate the effect of medications having anticoagulant properties.

12 Review the properties and effects of feverfew

Feverfew is used for fever, headache, and prevention of migraine headaches. At least 39 compounds within feverfew have been identified. It is not yet clear how feverfew works in the prevention of migraine. Laboratory evidence suggests that feverfew extracts might inhibit platelet aggregation and serotonin release from platelets and leukocytes. It may inhibit serum proteases and leukotrienes and block prostaglandin synthesis by inhibiting phospholipase, preventing the release of arachidonic acid.

13 Review the effects of St. John’s wort

St. John’s wort is used for the treatment of mild to moderate depression through impaired reuptake of serotonin, norepinephrine, and dopamine. As such, when taken in conjunction with selective serotonin reuptake inhibitors (SSRIs) prescribed by a physician, serotonin excess may be an undesired effect. Like SSRIs, St. John’s wort should also not be administered to patients on monoamine oxidase inhibitors and β-sympathomimetic amines such as pseudoephedrine). It may alter the metabolism of immunosuppressants (e.g., cyclosporin) and cancer chemotherapy by stimulating cytochrome P-450 3A4. Metabolism of such drugs as warfarin, NSAIDs, local anesthetics, alfentanil, and midazolam may be enhanced.

14 Since these medications appear to impair coagulation, how can their effect be evaluated clinically?

The best means for detecting a coagulation defect secondary to herbal medications is a properly taken clinical history. Especially important are questions related to the hemostatic response during previous surgeries. Also important are questions regarding bleeding tendencies such as easy bruising, gingival bleeding, or excessive bleeding following procedures such as dental extractions. Positive responses suggest the need for laboratory testing. The most commonly used measures of coagulation include the activated partial thromboplastin time, which evaluates the intrinsic system, the prothrombin time, which evaluates the extrinsic pathway, platelet count, and bleeding time. However, bleeding time, the most commonly used measure of platelet function, is subject to many variables and may not always be reliable. More reliable tests of platelet function are available but are expensive, time-consuming, and not appropriate for routine screening.

KEY POINTS: Herbal Supplements image

1. Herbal does not necessarily mean safe. Few controlled scientific data exist on the risks and benefits of herbal medications.
2. Always ask patients about herbal/alternative medications that they may be taking. Do not depend on them to volunteer that information.
3. In situations in which excessive bleeding may prove especially problematic or in the patient taking multiple supplements thought to have anticoagulant potential, it may be best to discontinue these medications for 2 to 3 weeks before surgery.
4. Coagulation defects secondary to herbal medicines may not be evident using standard laboratory studies.

15 What are current recommendations regarding discontinuing use of herbal medications before surgery?

Most patients will not admit to the use of herbal medications unless directly questioned. The use of herbal medications is not necessarily a contraindication to surgery. But, because the pharmacodynamic and pharmacokinetic features of most of these drugs have yet to be determined, it might be best to discontinue use of these agents and other over-the-counter medications as far in advance of surgery as possible. If regional anesthesia is planned and the patient is on prescribed medications with antiplatelet effects, it may be wise to discontinue the herbal supplements at least a week before surgery. However, it should be noted that the Second American Society of Regional Anesthesia Consensus Conference on Neuraxial Anesthesia and Antithrombotic Therapy has stated, “Herbal drugs, by themselves, appear to represent no added significant risk for the development of spinal hematoma in patients having epidural or spinal anesthesia.”

Finally, it may be of some comfort to clinicians who often do not see patients until just before surgery and do not have an opportunity to make the recommendation to discontinue such supplements before surgery that serious complications associated with use of herbal medications still appear to be distinctly rare events.

SUGGESTED READINGS

1. Horlocker T.T., Wedel D.J., Benzon H., et al. Regional anesthesia in the anticoagulated patient: defining the risks (the second ASRA Consensus Conference on Neuraxial Anesthesia and Anticoagulation). Reg Anesth Pain Med. 2003;28:172-197.

2. Kaye A.D., Kucera I., Sabar R. Perioperative anesthesia: clinical considerations of alternative medications. Anesthesiol Clin North Am. 2004;22:125-139.

3. Lee A., Chui P.T., Aun C.S., et al. Incidence and risk of adverse perioperative events among surgical patients taking traditional Chinese herbal medicines. Anesthesiology. 2006;105:454-461.

4. Scharbert G., Kalb M.L., Duris M., et al. Garlic at dietary doses does not impair platelet function. Anesth Analg. 2007;105:1214-1218.

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