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March 13, 2006

Anesthesia And Herbal Medicines - Hidden Hazards
M.J. McKeown, MD, FACOG, FACS and Alexandra Andrews

Commonly Used Herbs

"A little learning is a dangerous thing; drink deep, or taste not the Pierian spring: there shallow draughts intoxicate the brain, and drinking largely sobers us again "
Alexander Pope - An Essay on Criticism, 1709

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Herbal medicine is an ancient discipline and continues to have use in the broadest sense of the word medicine. However with the rise of medical science and its at times arrogant belief it knows everything there has been a loss of the knowledge of and use of these ancient, powerful and beneficial medicines. It is almost ironic that many modern medicines have an origin in the decoctions and chants of shamans of many areas of the world. It is a shame that these origins are not taught and it can be dangerous to not learn the interactions of some herbs and modern medicines

The history of herbal medicine stretches back to the Chinese texts in the time of the Yellow Emperor Huang Di in 2,697 BC. Hippocrates used herbal medicine in his practice and in the training of others. The Greek Dioscorides's Materia Medica is still one of the world's greatest references on herbs. Several commonly used medicines have herbal origins; morphine is a derivative of the opium poppy, digoxin is derived from the foxglove, quinine and quinidine are derived from the bark of the Cinchona trees.

The use of herbal products has increased in the United States as much as 380% in the past 10 years. More than 32% of perioperative patients use herbals, dietary supplements or both. The World Health Organization studies indicate that approximately 75% of the world's population uses botanical preparations for basic health care needs. The WHO review of the literature indicates that 121 prescription medications are produced directly from plant extracts.

Recent studies indicate that a large percentage of patients did not inform their physicians about herbal or dietary supplement use. Accumulating evidence shows that this lack of communication can lead to potentially lethal herbal-medication interactions. Currently there is incomplete regulation of herbals and dietary supplements and few specific investigations into the interactions with controlled prescription medications. Dietary supplements must be labeled as to content and can advertise they have healthful or nutritional properties but they cannot advertise any therapeutic benefits. There is no requirement that the labels warn of possible interactions with prescription medications or of any adverse side effects or contraindications. Research into these problems has been primarily non-North American in location and publication. The German Commission E is a government agency that regulates the German herbal products. The German Commission E Monographs: Therapeutic Monographs on Medicinal Plants is one of few scientific reviews and analysis. Henry VIII legalized traditional healers and herbalists in 1548. There are many herbal schools in the United States. Each State has different regulations.

Herbal medicine providers are known as herbalists. Herbalists focus on the whole environmental being of the person under treatment. They typically take extensive histories and make a comprehensive analysis of body processes such as appetite, digestion, elimination and sleep. The herbalist approach is of the Wholistic Medicine type. There are many herbal schools in the United States. Regulations for herbal practitioners differ state by state.

With little regulation or usage advice many consumers follow the ancient idea that if a little is good then more must be better. Herbs that are safe in recommended dosage amounts can become toxic and even lethal in larger amounts. An additional danger is related to the source of the herbals or supplements. Adverse reactions occur in greater degree in products imported from outside North America or Europe. Consumers also need to be cognizant of the sources of herbals and supplements and if they have any plant or pollen allergies related to any of these sources they should not use the products.

All users of herbals and supplements should research these possible warnings and then develop a printed list of herbals and supplements taken and their possible interactions to give to their health care providers! However this is not commonly done and one study showed that 70% of patients who used herbals did not tell their physicians. There are many reasons for this; first, often consumers do not consider herbal products as medications; second, patients do not need a prescription to purchase herbal products; third, many herbal products are marketed as natural and consumers then consider them safe. Providers are also to blame because many do not ask their patients about herbal medications.

There are three general areas of interaction of commonly used herbal products; first, Direct Interactions - intrinsic pharmacological effects; second, Pharmacodynamic Interactions - alteration of the action of conventional medications at effector sites; third, Pharmacokinetic Interactions - alteration of absorption, distribution, metabolism and elimination of conventional medications. Examples of such interactions are seen in commonly used herbal products.

An area where herbal - medication interactions can be fatal is in the perioperative area. However there is a large area of uncertainty in such interactions in the areas of perioperative physiologic changes and pre-, intra-, and post-operative medications.

The pharmacologic medication controls used during the intense perioperative times of a patient are continually undergoing change. This likely means that new interactions will occur and may only be diagnosed and evaluated at the time of some severe or fatal reaction. The American Society of Anesthesiologists recommends that use of all herbal products be discontinued two to three weeks before surgery. The guidelines of this organization are:
Avoid all herbal products if nursing or pregnant
Check facts about herbal product claims with a qualified health care professional
Discontinue herbal products if any unusual symptom occurs and discuss this with a qualified health care professional
Discuss all herbal use with a qualified health care professional
Purchase only herbal products that have been standardized in terms of known effects for a given dose
Read all of the label of herbal products carefully
Use caution when giving herbal products to children or older adults
Use only recommended products that are labeled with Scientific name of the herb
Manufacture date
Expiration date
Lot number
The address of the supplier

Commonly Used Herbs
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Echinacea is most commonly used to treat viral, bacterial or fungal infections, particularly of the respiratory tract. There is no specific study investigating the interactions with immunosuppressive drugs however caution is advised because of possibly diminished effectiveness of such medications In contrast to the immunostimulatory effects of short term use of Echinacea the long term (> 8 weeks) has a potential for immunosuppression and thus poor wound healing or opportunistic infections. The possibility of hepatotoxicity (if using seed extract) has been reported and patients taking this should discontinue it as far in advance of surgery as possible if any compromise of hepatic blood flow or function is anticipated. Echinacea inhibits liver CYP3A4 in vitro.
Ephedra contains alkaloids including ephedrine, pseudoephedrine, norephedrine, methylephedrine, and norpseudoephedrine. Ephedra causes dose dependent increases in blood pressure and heart rate. The predominant ephedrine is a noncatecholamine sympathomimetic agent that shows alpha1, beta1, and beta2 effects by direct action on adrenergic receptors and indirect release of endogenous norepinephrine. These effects have been associated with fatal cardiac and central nervous system events. Patients who are users of ephedra and anesthetized with halothane may be at increased risk of cardiac arrhythmias. Ephedra may cause hypersensitivity myocarditis with cardiomyopathy and myocardial lymphocyte and eosinophil infiltration. The long term use of ephedra can deplete endogenous catecholamine stores and lead to perioperative hemodynamic instability. The combined use of ephedra and monoaminoxidase inhibitors can result in life-threatening hyperpyrexia, hypertension and coma. The pharmacokinetics of ephedrine show it to have an elimination half-life of 5.2 hours with 70%-80% excreted unchanged in the urine.
Ginger contains anticoagulant components. Ginger inhibits platelet aggregation in vitro by acting as an inhibitor of arachidonic acid, epinephrine, and adenosine diphosphate (ADP) and collagen. However a placebo controlled study showed that although there was dose dependent reduction of thromboxane synthetase and prostaglandin synthetase there was no reduction in bleeding time, platelet counts or platelet function. However ginger administered orally prior to induction of anesthesia can be prophylactic for postoperative nausea and vomiting.
Parthenolide in feverfew inhibits platelet aggregation by decreasing the releaseA patient of serotonin and affects the protein kinase pathway. Patients with long term use (3.5 - 8 years) showed no difference in ADP and thrombin-stimulated platelet aggregation. However serotonin-induced platelet aggregation was reduced.
Chronic use of licorice can cause hypokalemia, pseudoaldosteronism, hypertension or arrhythmias. Licorice inhibits the CYP3A4 liver enzyme in vitro although the clinical significance is not known.
Wild cherry:
Wild cherry can inhibit the liver enzyme CYP3A4. The clinical significance of this effect is not known.
Chamomile inhibits the liver enzyme CYP3A4 in vitro. The clinical significance is not known.
Goldenseal inhibits the liver enzyme CYP3A4 in vitro. The clinical significance is not known.
Cat's claw:
Cat's claw inhibits the liver enzyme CYP3A4 in vitro. The clinical significance is not known.
Milk Thistle:
Milk Thistle is an herb that may be beneficial. It has liver protective effect in animals and may help prevent liver damage from hepatotoxic drugs such as excessive alcohol, phenothiazines, buteryphenones and acetaminophen.
Garlic inhibits platelet aggregation, reduces thromboxane, increases fibrinolytic activity, and increases streptokinase activated plasminogen activator-8,9. This appears to be dose-dependent and the effect of one of its constituents, ajoene, appears to be irreversible and may potentiate the effects of other platelet inhibitors prostacyclin, forskolin, indomethacin and dipyrimidamole. It also has the potential to lower blood pressure. The potential for irreversible platelet effects warrants discontinuing garlic well in advance of any surgery where bleeding may be a problem.
Ginkgo alters vasoregulation, acts as an antioxidant, modulates neurotransmitter and receptor activity and inhibits platelet activating factor. Terpenoids are thought to be responsible for the pharmacologic effects. The elimination half lives of terpenoids taken orally are 3 - 10 hours. This means ginkgo should be stopped at least 36 hours before surgery.
Most actions are associated with ginsenoides that belong to the steroidal saponins. The pharmacologic actions of ginseng are not well understood but the underlying mechanism seems to be similar to steroid hormones. This effect in relation to glucose metabolism is efficacious in Type 2 Diabetes however unintended hypoglycemia may occur in patients who have been fasted before surgery. Ginsenoides also inhibit platelet aggregation and prolong the coagulation times of thrombin and activated partial thromboplastin. In vitro ginsenoide Rg2 inhibits platelet aggregation, ginsenoide Ro inhibits the conversion of fibrinogen to fibrin18 and ginsenoide Rg3 inhibits platelet activating factor19.
This herb is widely used as an anxiolytic and sedative. Kavalactones appear to be the active pharmacologic agents. These have a dose dependent effect on the central nervous system including antiepileptic, neuroprotective, and local anesthetic properties. Kava may act as a sedative - hypnotic by potentiating gamma-aminobutryic acid (GABA) neurotransmission. Peak plasma levels occur 1.8 hours after oral intake and the elimination half-life is 9 hours. These data suggest that patients taking Kava should discontinue it at least 24 hours before surgery.
St John's Wort:
The active compounds are thought to be hypericin and hyperforin. The effects are through the inhibition of serotonin, norepinephrine, and dopamine reuptake by neurons. Use of this herb with serotonin reuptake inhibitors may create a syndrome of serotonin excess. Oral use leads to peak levels of hypericin and hyperforin of 6 and 3.5 hours respectively and their half-lives are 43.1 and 9 hours. The long half life makes this particularly risky in the perioperative period. St John's Wort also affects digoxin pharmacokinetics possibly through an effect on the P-glycoprotein transporter. St John's Wort can also inhibit the binding of naloxone to opioid receptors and this has raised a concern it may cause excessive sedation when combined with narcotics. It also may have monoamine oxidase inhibition (MAOI).
Sesquiterpenes are the primary pharmacologic agent. Valerian produces dose-dependent sedation and hypnosis. The effect appears to be mediated through the GABA neurotransmitter and receptor function. Thus it would be expected to potentiate sedative effects of anesthetics and adjuvants that act through the GABA system. Caution should be taken in discontinuing long term users since they may be physically dependent and undergo a benzodiazepinelike withdrawal. Such long term users should be tapered during several weeks before surgery. It is important to read the detailed label of any herbal sleep aid since most of them contain valerian.

This short discussion contains suggestions for information needed by the users of herbal medications and diet supplements and by the health care providers they interact with.

If one refers to Alexander Pope's admonition it is seen that it is possible that a little knowledge can be fatal or debilitating and that more complete information can be life saving.

It is the responsibility of both the user of herbal medications and nutritional supplements and the providers of healthcare to be aware of the possibility of problems in this area and communicate with each other such that most adverse reactions can be prevented.

It would seem prudent to include coverage of this subject in all health care provider schools and associated internship and residency programs. It would also be beneficial if this subject were taught to all teachers in the public and private educational systems such that this subject matter would be known to all persons from the fifth grade on.

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