HERBAL MEDICINES ANESTHETIC IMPLICATIONS

1. HERBAL MEDICINESANESTHETIC IMPLICATIONS M. Ron Eslinger CRNA, MA, APN www.aamsn.com

2. 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.

3. 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.

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

5. 35 year old for posterior spinal fusion. • St. John’s Wort

6. HERBAL MEDICINEHISTORY • Early archaeological evidence - Neanderthal • 16th Century Medicinal Plants • Scientific method and the marginalization of Herbal Medicine - 19th 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

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

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

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

10. Top Ten Selling Herbs1995 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)

11. 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

12. 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

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

14. 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

15. 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

16. 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

17. 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

18. ORGAN SYSTEM TOXICITY(from Winslow and Kroll, 1998) PULMONARY 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

19. 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

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

21. ECHINACEAEchinacea purpurea and angustifolia

22. ECHINACEAEchinacea 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

23. GINKGO Gingko biloba GINGKO Gingko biloba

24. GINKGOGingko 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

25. GINKGOGingko 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

26. St. John’s Wort

27. ST. JOHN’S WORTHypericum 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

28. 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

29. GARLICAllium sativum GARLICAllium sativum

30. GARLICAllium 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 (300mg TID)

31. GARLICAllium 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

32. GINSENG Asian Panax ginsengAmerican Panax quinquefoliusSiberian Eleutherococcus senticosus

33. GINSENG Asian Panax ginsengAmerican Panax quinquefoliusSiberian Eleutherococcus senticosus USES Adaptogen, mood and energy level enhancer, antioxidant, hypoglycemic MECHANISM ?augmentation of adrenal steroidogenesis via pituitary immunomodulation via increased IgG and IgM responses to primary and secondary challenges associated with increased interferon production enhancement of cell mediated immunity and natural killer cell activity hypoglycemic via ginsenoside Rb2 and panaxans I, J, K, and L

34. GINSENG Asian Panax ginsengAmerican Panax quinquefoliusSiberian 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 (>15g/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)

35. GINSENGAsian Panax ginsengAmerican Panax quinquefoliusSiberian 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

36. GOLDENSEAL Hydrasis canadensis Golden Seal

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

38. SAW PALMETTO Serenoa repens Saw Palmetto

39. 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-alpha-reductase activity STUDIES 2 double blind studies showed significant improvement in objective and subjective data versus placebo and finasteride

40. SAWPALMETTOSerenoa repens TOXICITY GI upset DRUG INTERACTIONS caution with hormonal therapies

41. VALERIAN Valeriana officinalis

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

43. VALERIANValeriana officinalis ANESTHETIC CONSIDERATIONS Will likely potentiate barbiturate and benzodiazepine effects (Should not be used with alcohol)

44. Feverfew FEVERFEW Tanacetum parthenium

45. FEVERFEWTanacetum parthenium USES Migraine MECHANISM Suppresses prostaglandin production by 86-88% (no anti-cyclooxygenase activity) ?parthenolide STUDIES shown effective in reducing number of episodes in 2 placebo-controlled, blinded studies of 17 and 72 patients

46. FEVERFEWTanacetum 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

47. GINGERZingiger oficinale

48. GINGERZingiger oficinale USES antinauseant antispasmodic MECHANISM not stated for primary use thromboxane synthetase inhibition STUDIES not found

49. GINGERZingiger 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

50. EPHEDRA Ephedra sinica