Herbal supplements and anesthesia

Herbal medicines have become enormously popular in recent years: nearly 20 million Americans are using herbal supplements for their purported health benefits including promotion of cardiac health, mental health, genitourinary health, and preventive health. These nutraceutical supplements are used in hopes of slowing the aging process, preventing the onset of dementia, lowering cholesterol, maintaining vision, enhancing immunity, and improving cardiovascular health. Society may be ingesting these supplements as an alternative to more expensive prescription drugs and as natural treatments with the goal of minimizing side effects that may accompany prescription medications. In 2007, Americans spent $34 billion on herbals and vitamins [1]. A recent survey revealed that the average person using supplements is older than 50 years, Caucasian, female, married, college-educated, and in a higher socioeconomic class [2].

Despite the common use of these agents, 70% of patients using these supplements neglect to tell their physician that they are taking them unless they are specifically asked. As a result, physicians may not be aware of potentially problematic substances and drug interactions of herbal medications with prescription drugs. Although these agents are often marketed as innocuous, the intake of these herbal medicines may pose health risks to patients.

The Dietary Health and Supplement Act of 1994 [3] defines herbal preparations as dietary supplements; therefore, they are not subject to the same rigorous safety and efficacy standards that prescription and over-the-counter medications must meet. For these supplements to be withdrawn from the market, the Food and Drug Administration (FDA) must prove a lack of safety [4].

Despite various salubrious effects of herbals, the possibility of detrimental side effects exists, especially when multiple supplements are used in combination. From 1985 to 1997, nearly 200 deaths were directly attributed to the use of herbal supplements [5]. Because the use of these dietary supplements is prevalent and increasing, an understanding of their possible interactions with commonly used anesthetic drugs as well as potential untoward effects is crucial for anesthesiologists and perioperative physicians.

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St John’s Wort

St John’s wort, derived from the flowering tops of the perennial plant Hypericum perforatum native to Europe and Asia, was brought to North America by European settlers. According to legend, the eponymous St John’s wort arose from the head of John the Baptist after his beheading. Patients may use this herb for its anxiolytic, sedative, bronchodilatory, and antidepressant effects, and as an analgesic for peptic ulcer disease and hemorrhoids [6]. Hyperforin and hypericin are believed to be 2 of the principal active constituents of St John’s wort responsible for its beneficial effects [7]. St John’s wort is available in a variety of preparations to treat various ailments. The suggested dose to treat depression is 300 mg, standardized to 0.3% hypericin, taken orally 3 times daily for 4 to 6 weeks; alternatively, a tea can be brewed from 2 to 4 g of the herb in 1 to 2 cups of water [7].

The mechanism of action of St John’s wort remains unknown, as in vitro and in vivo studies have reached different conclusions: in vitro studies demonstrate inhibition of monoamine oxidase isoforms, whereas in vivo studies demonstrate inhibition of γ-aminobutyric acid (GABA) receptors [8]. The antidepressant effects of the herbal may be a result of GABA inhibition. The potential for undesired side effects with concomitant administration of monoamine oxidase inhibitors (MAOIs), amphetamines, selective serotonin reuptake inhibitors (SSRIs), trazodone, tricyclic antidepressants, narcotics, and cold and flu medications exists [9]. Furthermore, St John’s wort has been implicated in one case of hypertensive crisis in a 41-year-old psychiatric patient [10].

Interactions with β-sympathomimetic agents such as Ma Huang or pseudoephedrine may instigate a hypertensive crisis. St John’s wort, when taken in combination with other SSRIs such as fluoxetine or paroxetine, may cause serotonergic syndrome, which is manifested by tremors, hyperthermia, autonomic dysfunction, hallucinations, myoclonus, and possibly death [11,13]. Photosensitivity is another common side effect of St John’s wort, therefore caution is advised when administering other drugs, such as tetracycline and piroxicam, which have similar adverse effects. In addition, caution is advised with patients concurrently using MAOIs. Further research is needed to elucidate the exact interactions and effects, but caution and awareness should be the rule in the perioperative period.

Echinacea

Echinacea is produced from the dried roots and rhizomes of the Echinacea angustifolia or Echinacea pallida plants. Fresh juice, made from the nonroot portions of the Echinacea purpurea plant, is also available [6]. Patients commonly take this herbal supplement to treat the following ailments: abscesses, eczema, burns, liver cancer [13], colorectal cancer [14], upper respiratory tract infections, urinary tract infections, varicose leg ulcers, and skin wounds [6].

Certain patient populations may not benefit from echinacea therapy: individuals infected with human immunodeficiency virus, patients with AIDS, patients with collagen vascular disease, and patients suffering from multiple sclerosis (echinacea stimulates the immune system [14], therefore autoimmune diseases that are treated with immunosuppressant drugs may have a negative interaction with echinacea).

Echinacea is an inhibitor of the cytochrome P-450 3A4 hepatic microsomal system, one of the key metabolic enzyme pathways involved in drug metabolism. This effect can become a concern in patients concomitantly taking drugs that are metabolized by this system, including phenytoin, rifampin, rocuronium, and local anesthetics; caution is advised because there may be prolonged clinical effects of these agents [15]. Awareness of this interaction is important for anesthesia providers.

Ginkgo Biloba

Prized by Chinese herbalists for centuries, Western interest in ginkgo as a nonpharmacologic treatment of Alzheimer disease has intensified lately as more and more people have become interested in alternative medicines and therapies [16]. Ginkgo extract is derived from the leaves of the kew tree, also known as the maidenhair tree or Ginkgo biloba tree. Patients use Ginkgo to treat such ailments as asthma, dementia, hearing loss, SSRI-induced erectile dysfunction, memory loss, and senile macular degeneration, and to enhance alertness [6]. In France and Germany, ginkgo is among the leading prescriptions for poor circulation and dementia, whereas in the United States ginkgo is available only as an over-the-counter dietary supplement [6]. Ginkgo is among the most popular herbal supplements in the United States, with sales exceeding $150 million [17].

Awareness of possible adverse effects of ginkgo is imperative for the anesthesiologist, as ginkgo is the third best-selling herbal product in the United States [15]. Although relatively safe, possible untoward effects of the herb include nausea, vomiting [18], headache, seizures, and increased risk of bleeding (the maximum recommended dose is 240 mg thrice a day). Furthermore, several case reports detailing morbidities of ginkgo exist: subarachnoid hemorrhage, subdural hematoma, and hyphema [19–22]. The additive effects of ginkgo with aspirin, warfarin, enoxaparin, heparin, abciximab, and other anticoagulant and antiplatelet agents may contraindicate neuraxial anesthetic techniques, as clotting ability may be unpredictable. The terpene lactone components of ginkgo (ginkgolides) inhibit blood clotting via inhibition of platelet aggregation [21,23]. Perioperative physicians may better assess the degree to which a patient is anticoagulated using platelet function analysis and/or coagulation studies. Common drug interactions include a decreased efficacy of anticonvulsants when administered with ginkgo [23]. Also, the seizure threshold is lowered in patients taking tricyclic antidepressants with ginkgo [23]. It is recommended that gingko be discontinued 36 hours before surgery to decrease the risk of side effects [24].

Saw Palmetto

Saw palmetto is harvested from the brown-black berries of the American dwarf palm, Serenoa repens/Sabal serrulata. Historically, saw palmetto was listed as a treatment for genitourinary tract ailments in the National Formulary from 1906 to 1950 [6]. At present, patients use saw palmetto to treat benign prostate hypertrophy (BPH), to decrease gynecomastia [6], to improve libido, to increase sperm production, and to reduce fluid retention.

Possible concerns for the anesthesiologist and perioperative physician include an elevation in blood pressure and a theoretical potentiation of blood-thinning agents [6].

Garlic

Garlic, botanically known as Allium sativum, is one of the most studied medicinal herbs. The use of garlic to treat various maladies has been traced back not only to the ancient China but also to western Europe [25]. Supplements of garlic are prepared from either dried cloves that have been crushed into powder or are made from garlic oil. Of note, products that claim to be “odor-free” may lack medicinal value, because it appears that the beneficial effects of garlic come from the sulfur-containing allicin, the chemical that imparts garlic with its distinctive aroma [6]. Garlic has been used to treat asthma, tinea pedis, constipation, diabetes, fungal infection, heavy-metal poisoning, hypertension, and hypercholesterolemia [6].

The commonly recommended dose of garlic for treating elevated cholesterol is 600 to 900 mg orally once daily [6]. Alternatively, 4 g of fresh garlic or 8 mg of garlic oil can be taken. The World Health Organization (WHO) 1999 monograph recommends these doses: 2 to 5 g fresh garlic, 0.4 to 1.2 g dried powder, 2 to 5 mg oil, 300 to 1000 mg extract, or any other formulation containing 2 to 5 mg allicin [6]. The formulation of garlic most often used in clinical trials is Kwai (Lichtwer Pharma, Köln, Germany); it is available as a nonenteric-coated dehydrated garlic powder formulation standardized for 1.3% allicin.

Garlic impairs platelet aggregation and has been associated with reports of bleeding. Based on this fact it should be used cautiously, if at all, in patients with peptic ulcer disease or intracranial bleeding, and in patients receiving concurrent antiplatelet or anticoagulation therapy or nonsteroidal anti-inflammatories, or with other drug-related hemostatic issues [26]. There is a case report of a spontaneous spinal/epidural hematoma in a patient using excessive amounts of garlic [27]. Other important adverse effects of garlic include dizziness, nausea, asthma exacerbations, hypothyroidism, and exacerbation of gastroesophageal reflux disease [6].

Garlic’s effect on platelet aggregation is complex and is caused by several mechanisms: garlic reduces thromboxane formation from arachidonic acid, inhibits phospholipase activity, and inhibits the incorporation of arachidonate into platelet phospholipids [28,29].

The anesthesiologist caring for patients being treated with garlic therapy should be especially cognizant for surgical hemostasis. Physicians should be vigilant perioperatively for the possibility of excessive bleeding both intra- and postoperatively [28]. Furthermore, garlic has been reported to interact with the P450 enzyme system [30], which also may affect concomitant drug metabolism.