HERBAL MEDICINES ANESTHETIC IMPLICATIONS M Ron Eslinger CRNA

HERBAL MEDICINES ANESTHETIC IMPLICATIONS M. Ron Eslinger CRNA, MA, APN www. aamsn. com

A 35 year old athletic woman with a history of migraines presents for ACL reconstruction. Her only pertinent history is previous PONV after 3 GA’s for gynecologic procedures. She completed a preop screening form and consultation in the preop clinic was deferred. She indicates multivitamin use on her questionnaire. She is very motivated to avoid PONV this time.

A 35 year old otherwise healthy mother of three presents for posterior lumbar fusion for chronic back pain that has failed conservative treatment. Because of her unremarkable history, her consultation in preop clinic was deferred. She is attended by her mother as she and her spouse are separated.

A 35 year old athletic woman with a history of migraines presents for ACL reconstruction. History of PONV. Feverfew Ginger

35 year old for posterior spinal fusion. St. John’s Wort

HERBAL MEDICINE HISTORY • Early archaeological evidence - Neanderthal • 16 th Century Medicinal Plants • Scientific method and the marginalization of Herbal Medicine - 19 th Century • Rebirth of herbal medicine and natural health in the 1960’s • Establishment of Office of Alternative Medicine, National Institutes of Health 1992 • 1994 FDA Dietary Supplement and Health Education Act

HERBAL MEDICINE EPIDEMIOLOGY • 3 - 93% of U. S. population use herbals • Generally higher internationally

Incidence of Herbal Medicine Use Among Age Groups % Age group Tsen, et al, Alternative medicine Use in Presurgical Patients, Anesthesiology, 93, 148 -51

n=3106 Tsen, et al, Alternative medicine Use in Presurgical Patients, Anesthesiology, 93, 148 -51

Top Ten Selling Herbs 1995 Survey of 163 Health Food Retail Stores (Winslow and Kroll, 1998) ECHINACEA GARLIC GOLDENSEAL GINSENG GINKGO SAW PALMETTO ALOE MA HUANG SIBERIAN GINSENG CRANBERRY (ST. JOHN’S WORT, VALERIAN, FEVER FEW)

ECONOMICS AND REIMBURSEMENT • • • $553 million in 8000 health food stores - 1994 $ 1. 2 billion from all sources 20% annual growth rate largest growth area in retail pharmacies increasing coverage of herbals and alternative therapies by insurance and managed care industries

QUALITY CONTROL 1994 Dietary Supplement and Health Education Act Compromise act No requirements for: Proof of efficacy Proof of safety Standards for quality control Cannot promise a specific cure, but may claim effect Burden of proving product unsafe lies with FDA

QUALITY CONTROL • Variability between manufactures and batches • Potency affected by growing conditions, storage, handling, and preparation - up to 10, 000 fold difference in potency

QUALITY CONTROL • Inaccuracy of labels • Contamination with other substances – Mandrake(scopolamine) or Snakeroot (reserpine) in Ginseng preparations – Use of additives not found on label (NSAID’s, steroids, antibiotics, sedatives, hypnotics) – Belladonna poisoning in herbal tea (NYC) – Digitalis intoxication from mislabeled plant extract – Heavy metals (lead, arsenic, cadmium, copper, mercury) in preparations from some foreign countries

EFFICACY AND SAFETY • No profit in conducting controlled studies in U. S. • Reported effects stem from anecdotal reports and a few well controlled clinical trials • System for reporting ADR’s for herbals and dietary supplements is poor (FDA web site available at: http: //www. fda. gov • Potential safety issues include: – Drug-herb interactions – Herb-body interactions (inhibition or stimulation of microsomal liver enzymes) – Toxicity from contaminants – Delayed intervention with allopathic treatment

ORGAN SYSTEM TOXICITY (from Winslow and Kroll, 1998) GASTROINTESTINAL HEPATOTOXIC (MILD TO SEVERE) Chinese herbal teas, Mistletoe, Germander, Chaparral, Comfrey NAUSEA/VOMITTING Dandelion, Garlic, Ginseng, Chaparral DIARRHEA Herbal teas, Aloe, Ligustrum, Dandelion, Prunelia, Garlic, Ginseng HEMATOLOGIC ANTICOAGULANT/ANTIPLATELET Yarrow, Red clover, Tang-kuei, Pau d’arco, Salvia

ORGAN SYSTEM TOXICITY (from Winslow and Kroll, 1998) CENTRAL NERVOUS SYSTEM NERVOUSNESS / AGITATION/INSOMNIA / MOOD CHANGES DEPRESSION / CONFUSION / HALLUCINATIONS Ginseng (long-term and higher doses) HALLUCINOGENIC Catnip, Hops, Kava kava, Khat, Lobelia, Mandrake, Nutmeg, Jimson weed, Valerian, Yohimbe CHOLINERGIC TOXICITY (CONTAINS ATROPINE, SCOPOLOMINE, HYOSCYAMINE) Jimson weed SEDATION Peony, Salvia, Tang-kuei SEIZURES / PSYCHOSIS / COMA Ephedra

ORGAN SYSTEM TOXICITY (from Winslow and Kroll, 1998) PULMONARY HYPERTENSION Chinese herbal teas ALLERGIC / IMMUNOLOGIC CONTACT DERMATITIS Propolis, Garlic, Echinacea, Melaleuca oil SYSTEMIC LUPUS ERYTHEMATOSIS Alfalfa RENAL DIURESIS Burdock, Astragalus, Peony, Dandelion HYPERTENSION / SODIUM AND WATER RETENTION / HYPOKALEMIA Licorice, Glycyrrhiza glabra, Glycyrrhiza radix

ORGAN SYSTEM TOXICITY (from Winslow and Kroll, 1998) ENDOCRINOLOGIC GYNECOMASTIA / VAGINAL BLEEDING Ginseng (estrogen-containing) GOITERS / HYPERTHYROIDISM / HYPOTHYROIDISM Kelp (iodine-containing) INHIBITION OF IODINE UPTAKE Garlic HYPOGLYCEMIA Atractylodes, Scrofularia, Lycium, Burdock

ORGAN SYSTEM TOXICITY CARDIOVASCULAR HYPOTENSION Astragalus, Codonopsis, Prunella, Scrofularia, Salvia HYPERTENSION Ginseng HYPERTENSION / CORONARY SPASM / PALPITATIONS Ephedra

• ECHINACEA Echinacea purpurea and angustifolia

ECHINACEA Echinacea purpurea, pallida, and angustifolia USES Immune system stimulant (E. augustifolia) Anti-infective (E. pallida) Wound healing (E. purpurea) MECHANISM Alkylamide and polysaccharide consituents result in immunostimulation secondary to enhanced phagocytosis and non-specific T-cell stimulation in vitro and in vivo. STUDIES 1) Decrease in flu-like symptoms from 10 to 7 days 2) 15% reduction in number of colds TOXICITY tachyphylaxix, ? hepatotoxicity, shivering, fever, weakness, potential cross allergy with daisy and sunflower families, autoimmune exacerbations

GINKGO Gingko biloba GINGKO Gingko biloba

GINKGO Gingko biloba USES Antioxidant, Enhances Cerebral Blood Flow, Reduces symptoms of peripheral vascular disease and Raynaud’s, Alleviates vertigo and tinnitus MECHANISM Ginkgolides antagonize PAF(gingkolide B) antioxidant activity of flavenoid, terpenoids, organic acids STUDIES 1) improvement in 2 of 3 clinical parameters of cognitive function at 12 weeks in 309 pateients in placebo controlled study 2) improvement in two tests of cognitive function in 2020 Alzheimer’s patients with no difference in adverse effects compared to placebo

GINKGO Gingko biloba TOXICITY GI upset, headache spontaneous hyphema (case report) spontaneous bilateral subdural hematomas (case report) ? neurotoxicity (gingkotoxin in both leaf and seed) POTENTIAL DRUG INTERACTIONS NSAID’s, aspirin, anticoagulants ANESTHETIC CONSIDERATIONS Regional anesthesia, preoperative bleeding history, ? labs, intraoperative bleeding

St. John’s Wort

ST. JOHN’S WORT Hypericum perforatum USES Antidepressant for mild to moderate depression Possible anti-inflammatory and anti-viral activity MECHANISM 10 constituents which may contribute to pharmacoloical effects (naphthodianthroms, flavonoids, xanthose, bioflavonoids) weak MAOI or selective serotonin reuptake inhibition STUDIES Hypericum extracts superior to placebo and equivalent to amitriptyline or imipramine with less side effects in meta analysis of 1757 patients

ST. JOHN’S WORT Hypericum perforatum TOXICITY photosensitivity (hypericin) MAOI (NIH sponsored study ongoing) possibly serotonism (headache, sweating, dizziness, agitation) DRUG INTERACTIONS beta-symphathomimetics, ephedra, meperidine, serotonin reuptake inhibitors, photosensitizing medications ANESTHETIC CONSIDERATIONS as above, ? discontinue prior to surgery may prolong effects of anesthesia

GARLIC Allium sativum

GARLIC Allium sativum USES Antispasmodic, antiseptic, bacteriostatic, antiviral, promotor of leukocytosis, hypotensive, hypocholesterolemic MECHANISM not stated inhibition of epinephrine induced in vitro platelet aggregation STUDIES hypotensive effect in many animal studies modest decrease in serum cholesterol and triglycerides in human studies using large doses (300 mg TID)

GARLIC Allium sativum TOXICITY inhibition of spermatogenesis in rats decreased platelet aggregation with one case report of spontaneous spinal epidural hematoma in an 87 yo man elevated INR DRUG INTERACTIONS antiplatelet agents warfarin potentiation ANESTHETIC CONSIDERATIONS as above

GINSENG Asian Panax ginseng American Panax quinquefolius Siberian Eleutherococcus senticosus

GINSENG Asian Panax ginseng American Panax quinquefolius Siberian Eleutherococcus senticosus USES Adaptogen, mood and energy level enhancer, antioxidant, hypoglycemic MECHANISM ? augmentation of adrenal steroidogenesis via pituitary immunomodulation via increased Ig. G and Ig. M responses to primary and secondary challenges associated with increased interferon production enhancement of cell mediated immunity and natural killer cell activity hypoglycemic via ginsenoside Rb 2 and panaxans I, J, K, and L

GINSENG Asian Panax ginseng American Panax quinquefolius Siberian Eleutherococcus senticosus STUDIES animal studies of immune effects Double-blind, placebo controlled study of 36 type II diabetics revealed subjective improvement in mood, vigor, well-being, decreased weight and increased physical activity, and moderately lower fasting serum glucose TOXICITY Ginseng abuse syndrome (>15 g/day) - sleepiness, hypertonia, edema hypertension, insomnia, vomiting, headache, epistaxis Stevens-Johnson Syndrome (case report) Vaginal bleeding with oral and topical use (case reports) Mastalgia and diffuse breast nodularity (case report) ? fetal adrogenization (Siberian ginseng) (case report)

GINSENG Asian Panax ginseng American Panax quinquefolius Siberian Eleutherococcus senticosus DRUG INTERACTIONS Possible interaction with antiplatelet drugs and anticoagulants based on case report of decreased INR in patient on warfarin Possible potentiation of CNS stimulants or excacerbations of manic or psychotic symptoms in predisposed individuals ANESTHETIC CONSIDERATIONS as related to above

Golden Seal GOLDENSEAL Hydrasis canadensis

GOLDEN SEAL Hydrasis canadensis USES Diuretic Anti-inflammatory Laxative Hemostatic TOXICITY / PRECAUTIONS Oxytotic (pregnancy) Overdose may cause paralysis Aquaretic (not diuretic) May worsen edema and/or hypertension

SAW PALMETTO Serenoa repens Saw Palmetto

SAW PALMETTO Serenoa repens USES Benign prostatic hypertrophy Diuretic, urinary antiseptic, anabolic MECHANISM antiandrogenic acivity of hexane extract inhibits binding of dihydrotestosterone at receptors and 5 -alphareductase activity STUDIES 2 double blind studies showed significant improvement in objective and subjective data versus placebo and finasteride

SAW PALMETTO Serenoa repens TOXICITY GI upset DRUG INTERACTIONS caution with hormonal therapies

Valeriana officinalis

VALERIAN Valeriana officinalis USES Mild sedative Mild anxiolytic MECHANISM not stated STUDIES decreased sleep latency in 2 studies, one showing mild EEG changes suggesting hypnotic effect

VALERIAN Valeriana officinalis ANESTHETIC CONSIDERATIONS Will likely potentiate barbiturate and benzodiazepine effects (Should not be used with alcohol)

Feverfew FEVERFEW Tanacetum parthenium

FEVERFEW Tanacetum parthenium USES Migraine MECHANISM Suppresses prostaglandin production by 86 -88% (no anticyclooxygenase activity) ? parthenolide STUDIES shown effective in reducing number of episodes in 2 placebocontrolled, blinded studies of 17 and 72 patients

FEVERFEW Tanacetum parthenium TOXICITY GI irritation or aphthous ulcerations in 5 -15% Inhibits platelet activity Rebound headaches Post-feverfew syndrome - nervousness, tension, headache, insomnia, stiffness, joint pain, tiredness DRUG INTERACTIONS anti-platelet agents, anticoagulants ANESTHETIC CONSIDERATIONS bleeding history, ? labs, discontinue preop

GINGER Zingiger oficinale

GINGER Zingiger oficinale USES antinauseant antispasmodic MECHANISM not stated for primary use thromboxane synthetase inhibition STUDIES not found

GINGER Zingiger oficinale TOXICITY potent inhibitor of thromboxane synthetase - bleeding DRUG INTERACTIONS NSAID’S, aspirin, anticoagulants ANESTHETIC CONSIDERATIONS Bleeding history, ? preop labs, intraop bleeding Discontinue prior to surgery

EPHEDRA Ephedra sinica

EPHEDRA (MA HUANG) Ephedra sinica USES Diet aid Bacteriostatic Antitussive MECHANISM release of endogenous catecholamines (indirect sympathomimetic) STUDIES Not found

EPHEDRA (MA HUANG) Ephedra sinica TOXICITY hypertension (mild to severe), tachycardia, cardiomyopathy, dysrhythmia, MI, CVA, seizure, psychosis, death DRUG INTERACTIONS MAOI’s, cardiac glycosides, halothane, oxytotics ANESTHETIC CONSIDERATIONS Discontinue prior to surgery As related to above

World Wide Web Resources Organization Address FDA http: //www. fda. gov Links MEDWATCH special nutritionals adverse event monitoring system American Botanical Council http: //www. herbs. org Herb Research Foundation University of http: //www. nnlm. MEDLINE, pictures Washington nih. gov Medicinal Herb Garden

Winslow and Kroll, Herbs as Medicines, Archives of Internal Medicine, 158, 2192 -2199. Miller, L. , Herbal Medicinals: Selected Clinical Considerations Focusing on Known or Potential Drug. Herb Interactions, Archives of Internal Medicine, 158, 2200 -2211. Murphy, Preoperative Considerations with Herbal Medicines, AORN Journal, 69(1), 173 -183. Tsen, et al, Alternative Medicine Use in Presurgical Patients, Anesthesiology, 93, 148 -151.

World Wide Web Resources American Botanical Council www. herbalgram. org NIH Office of Alternative Medicine altmed. od. nih. gov U. S. Dept of HHS www. healthfinder. gov (search “alternative medicine”) U. S. Pharmacopeia www. usp. org