Herbals And Anesthesia: An Unsafe Concoction Robert C. Jones, M.D. Staff Anesthesiologist Southern Maryland Anesthesia Associates Doctors Community Hospital 12 April 2007 Copyright (C) 2007 Robert C. Jones, M.D.

Real Life O.R. Cases n 1998: 30 year old patient for emergency surgery; BP 250s/140s; required multiple antihypertensives including nitroglycerin iv; postop, admitted to ephedra use

Copyright (C) 2007 Robert C. Jones, M.D. Real Life O.R. Cases n 1998: 30 year old patient for emergency surgery; BP 250s/140s; required multiple antihypertensives including nitroglycerin iv; postop, admitted to ephedra use n 2002: patient undergoing oral surgery; massive, unexpected bleeding; postop, admitted to ginseng use

Copyright (C) 2007 Robert C. Jones, M.D. Real Life O.R. Cases n 1998: 30 year old patient for emergency surgery; BP 250s/140s; required multiple antihypertensives including nitroglycerin iv; postop, admitted to ephedra use n 2002: patient undergoing oral surgery; massive, unexpected bleeding; postop, admitted to ginseng use n 2002: “Garlic Man”: patient undergoing TKR; known garlic use, but case proceeded because patient was air-evac from Italy; massive bleeding despite tourniquet; required transfusion

Copyright (C) 2007 Robert C. Jones, M.D. Real Life O.R. Cases n 1998: 30 year old patient for emergency surgery; BP 250s/140s; required multiple antihypertensives including nitroglycerin iv; postop, admitted to ephedra use n 2002: patient undergoing oral surgery; massive, unexpected bleeding; postop, admitted to ginseng use n 2002: “Garlic Man”: patient undergoing TKR; known garlic use, but case proceeded because patient was air-evac from Italy; massive bleeding despite tourniquet; required transfusion n 2004: Young woman for appy: 1 liter blood loss (willow bark)

Copyright (C) 2007 Robert C. Jones, M.D. Real Life O.R. Cases n 1998: 30 year old patient for emergency surgery; BP 250s/140s; required multiple antihypertensives including nitroglycerin iv; postop, admitted to ephedra use n 2002: patient undergoing oral surgery; massive, unexpected bleeding; postop, admitted to ginseng use n 2002: “Garlic Man”: patient undergoing TKR; known garlic use, but case proceeded because patient was air-evac from Italy; massive bleeding despite tourniquet; required transfusion n 2004: Young woman for appy: 1 liter blood loss (willow bark) n 2007: Patient undergoing elective back surgery; intraop and postop: massive, unexpected bleeding/oozing; patient had taken multiple herbals until 12 days prior to surgery

Copyright (C) 2007 Robert C. Jones, M.D. Real Life Tragedy 2 Capsules of Cytodyne's Xenadrine contains: 335mgs of MaHuang 910mgs of Guarana 105mgs of White Willow Bark 125mgs of Citrus Aurantium (snyephrine) 100mgs of Acetyl L Carnitine 80mgs of L Tyrosine 50mgs of Ginger Root 40mgs of B5 Ingredients (including grammatical errors) from: Feb 17, 2003: 23 YO pitcher dies at Orioles training camp in Ft. Lauderdale; lawsuit by family alleges death caused by Xenadrine ® brand ephedra (Ma Huang)

Copyright (C) 2007 Robert C. Jones, M.D.

Oral/Maxillofacial Surgeons are Concerned as well...

Copyright (C) 2007 Robert C. Jones, M.D. Overview n Herbal Medicinals: “All Natural” and 0% FDA approved n A Little Something Extra with your Herbals, Ma’am? n Pharmacokinetics vs. Pharmacodynamics n Specific Herbals with Potential for Serious Interactions n Official Guidelines/Statements on Herbals + Anesthesia n So How Long Should Surgery be Postponed? n Questions

Copyright (C) 2007 Robert C. Jones, M.D. “All Natural” = Safe? n Examples of 100% Natural Substances: u Uranium u Anthrax u Puffer fish poison (tetrodotoxin) u Smallpox u Destroying Angel and Death Cap mushrooms u Cobra venom n Many of our most potent (and potentially deadly) prescription drugs come from herbs: e.g., digitalis from foxglove

Copyright (C) 2007 Robert C. Jones, M.D. Herbals are Not Regulated by the FDA n The dietary supplement industry lobbied Congress hard to pass the 1994 Dietary Supplement Health Education Act (DSHEA), which treats DS as food, rather than as drugs n “The 1994 Dietary Supplement Act does not require that dietary supplements (defined broadly to include many substances, such as herbs and amino acids, that have no nutritive value) be shown to be safe or effective before they are marketed. The FDA does not scrutinize a dietary supplement before it enters the marketplace. The agency is permitted to restrict a substance if it poses a "significant and unreasonable risk" under the conditions of use on the label or as commonly consumed.” --Former FDA Commissioner David A. Kessler, MD, JD, in a June, 2000 New England Journal of Medicine Editorial

Copyright (C) 2007 Robert C. Jones, M.D. A little something extra with your Herbals?

Copyright (C) 2007 Robert C. Jones, M.D. A little something extra with your Herbals? n Substances found in herbal preparations available over the counter in the USA: u carcinogens (hexachlorobenzene, quintozene) u pesticides (including OCPs) u heavy metals (lead, mercury, arsenic, cadmium) u sawdust u male enhancement and other prescription drugs u mold and other fungi u little or no active ingredient

Copyright (C) 2007 Robert C. Jones, M.D. Quality Control, Schmality Control n Many scientific assays of dietary supplements/herbals have found major problems: u Variability in product dosage, even from lot to lot by the same manufacturer u Little or no active ingredient u Massive contamination u Prescription drugs mixed in

Copyright (C) 2007 Robert C. Jones, M.D. (web quotes from

Copyright (C) 2007 Robert C. Jones, M.D. Pharmacokinetics and Pharmacodynamics of Herbals There will be a test on the next slide following this lecture...

Copyright (C) 2007 Robert C. Jones, M.D. From:

Copyright (C) 2007 Robert C. Jones, M.D. Pharmacokinetics and Pharmacodynamics of Herbals n Pharmacokinetics: What the body does with a drug n Depends on known quantity of drug administered n Problem: Unknown interactions between dozens/hundreds of substances in some herbal mixes (risk of adverse interaction increases asymptotically after 8-10 drugs) n Problem: Lack of standardization of herbals plus polypharmacy of mixtures makes physician prediction of plasma levels or total dose (area under the curve) impossible for most preparations.

Copyright (C) 2007 Robert C. Jones, M.D. Anyone care to speculate on the clearance of all of these?

Copyright (C) 2007 Robert C. Jones, M.D. Pharmacokinetics and Pharmacodynamics of Herbals n Pharmacodynamics: What a drug does to the body n Downregulation of receptors, altered renal physiology, platelet effects (thrombasthenia), and/or hepatotoxicity can take weeks to resolve after herbal use stops n “I stopped using alcohol two days ago, so I’m O.K.”: maybe, maybe not... (DTs anyone?)

Copyright (C) 2007 Robert C. Jones, M.D. Specific Bad Herbals n Cardiac Toxicity: u Ephedra, licorice, black cohosh, goldenseal (via aquaretic effect); all weight loss products; guarana (caffeine); nitric oxide stimulants n Bleeding: u “The Bad Gs”: Garlic, Ginseng, Ginkgo Biloba, Ginger u Also: feverfew, echinacea, vitamin E n Hepatotoxicity: u Black cohosh, Echinacea, kava kava, chapparal leaf, comfrey n Synergism with sedatives/anesthetic agents: u St. John’s Wort, valerian, kava kava n Interference with drug metabolism/P450 system induction u Numerous herbals

Copyright (C) 2007 Robert C. Jones, M.D. Ephedra: worst of the worst n Also known as ma huang (“yellow horse”), ephedra sinica, desert tea, etc. n Primary active ingredients ephedrine and pseudoephedrine n Risk of cardiac toxicity, arrhythmias, sudden death, severe hypertension, interaction with MAOIs, interaction with oxytocin (hypertension) n Withdrawn from market in U.S. in 2004 by FDA order...or was it?

Copyright (C) 2007 Robert C. Jones, M.D. Looking for ephedra in all the wrong places

Copyright (C) 2007 Robert C. Jones, M.D. Bleeding: Not just for the Middle Ages anymore n “The Bad Gs”: ginger, garlic, ginkgo, ginseng, plus feverfew, echinacea and vitamin E n Will only affect INR if patient on warfarin; also have inherent effects on platelet function n NO TEST can reliably predict surgical bleeding from platelet inhibition (template bleeding time is useless: Semin Thromb Hemost Jan;16[1]:1-20) n Risk to patients: Intraoperative hemorrhage; needless exposure to blood products and potential pathogens; postoperative “oozing” requiring hematoma evacuation, etc.

Copyright (C) 2007 Robert C. Jones, M.D. Hepatotoxicity u Black cohosh, Echinacea, kava kava, chapparal leaf, comfrey; many Asian herbal tea concoctions u Potential to decrease markedly hepatic metabolism of anesthesia “poisons” perioperatively u Can lead to... Fulminant hepatic failure associated with the use of black cohosh: a case report. Liver Transpl Jun;12(6):989-92

Copyright (C) 2007 Robert C. Jones, M.D. Interactions with Anesthetics/Sedatives n St. John’s Wort, valerian, kava kava n Potential for anesthetic overdose/post-operative sedation and/or respiratory depression from CNS effects of these herbals n Delayed emergence from general anesthesia has been reported from St. John’s Wort (Anesthesiology:Volume 96(4)April 2002pp )

Copyright (C) 2007 Robert C. Jones, M.D. Interference with drug effects n Numerous herbals induce the cytochrome P450 (CYP) system or other hepatic enzymes, thus reducing effects of: u Protease inhibitors for HIV u Corticosteroids u Transplant rejection prevention drugs (cyclosporin) u Digoxin u Many anesthetic drugs

Copyright (C) 2007 Robert C. Jones, M.D. Recommendations: ASA (American Society of Anesthesiologists) n “Natural” doesn’t always mean safe. Many herbal products on the market can cause harmful side effects or interact with your other medicines and anesthetics. n To prevent unforeseen complications, it is imperative that health care providers as well as patients become aware of the interactions of these products and that herbal use habits become a part of a patient’s documented history and treatment plan. n Herbs and other dietary supplements do not undergo the same strict research requirements as prescription drugs and are not subject to FDA testing before being put on store shelves. n Patients should tell their physicians – and physicians should ask – about all herbal, dietary or other over-the-counter preparations as well as prescription medicine that the patient is taking.

Copyright (C) 2007 Robert C. Jones, M.D. Recommendations: AANA (American Association of Nurse Anesthetists) n STOP taking the herbal product at least two weeks prior to the scheduled procedure or surgery to prevent side effects. n Inform your surgeon and anesthesia provider that you are taking an herbal product. n Offer accurate information about any herbal products you are taking. n When asked about your medication history, include all herbal products, over- the-counter drugs, dietary supplements, minerals, and teas. n If you are not sure of the contents of an herbal product, then bring the product and the container it comes in with you for the preoperative anesthesia interview. n Make sure that someone close to you is aware that you take an herbal product. In the event that you need emergency care, this person will need to share this information with your healthcare providers. n Realize that herbal products need to be treated as medicine. Even if the product is natural, it still may be harmful when combined with anesthetics.

Copyright (C) 2007 Robert C. Jones, M.D. Recommendations: ACS (American Cancer Society) n The American Cancer Society (ACS) advises the public to be cautious of dietary supplements: Don't depend on promoters -- promises, or on people's stories of success. Learn as much as you can from reputable, expert sources about any herbal remedy you consider taking, and about its possible benefits or dangers. n Following is a list of guidelines offered by the ACS: n Rule One: Investigate before you buy or use. There are many resources in food stores, pharmacies, libraries and on the Internet. However, much of this information is produced by promoters and it contains biased or incorrect information. Rely on materials developed by trained experts in botanical medicine or the study of herbs. n Rule Two: Check with your doctor before you try an herbal medicine. He or she may or may not be thoroughly versed in all herbals, but hopefully your doctor will help you make a safe choice. n Rule Three: Do not take an herbal remedy instead of the medicine prescribed by your doctor without discussing it first. n Rule Four: Avoid herbal remedies if you are pregnant or breast feeding. n Rule Five: Don't depend on any herbal to cure cancer or any other serious disease. It won't, regardless of claims you might hear.

Copyright (C) 2007 Robert C. Jones, M.D. So How Long Does the Patient Have to be off of Herbals Preop?

Copyright (C) 2007 Robert C. Jones, M.D. So How Long Does the Patient Have to be off of Herbals Preop? n The surgeon and the patient should discuss the patient’s herbal use with anesthesiologist/nurse anesthetist (because the surgeon asked in the office, right?) n How invasive is procedure? MAC vs. General vs. Regional anesthesia; toe surgery vs. hysterectomy/AAA n Urgent/Emergent operations: obviously will proceed; may involve increase risk to patient n Elective procedures: recommendation in literature varies from 2 weeks to 1-2 weeks; explanation of the PANOYA syndrome and its interrelationship with excessively concrete thinking n Best advice: Patient safety would be promoted by adhering to a flat rule of 2 weeks (14 days) for the worst herbals; a few (e.g., saw palmetto) are relatively benign; need to weigh risk/benefit ratio

Copyright (C) 2007 Robert C. Jones, M.D. References