HERBAL MEDICINESHERBAL MEDICINESANESTHETIC IMPLICATIONSANESTHETIC 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 MEDICINEHERBAL MEDICINEHISTORYHISTORY

• 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

HERBAL MEDICINEHERBAL MEDICINEEPIDEMIOLOGYEPIDEMIOLOGY

• 3 - 93% of U.S. population use herbals

• Generally higher internationally

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

Incidence of Herbal Medicine Use Among Age Groups

%

Age group

0

5

10

15

20

25

30

<20 20-30 31-40 41-50 51-60 61-70 71-80 >80

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

n=3106

0

1

2

3

4

5

6

7

8

% o

f pa

tien

ts u

sing

her

b

Aloe Cranberry Echinacea Garlic Ginkgo biloba Ginseng Goldenseal Saw palmetto St. John's ort

Herb

Herbal medication use

Top Ten Selling HerbsTop 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)

ECONOMICS AND REIMBURSEMENTECONOMICS 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 CONTROLQUALITY 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 CONTROLQUALITY CONTROL

• Variability between manufactures and batches• Potency affected by growing conditions,

storage, handling, and preparation - up to 10,000 fold difference in potency

QUALITY CONTROLQUALITY 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 SAFETYEFFICACY 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 TOXICITYORGAN 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 TOXICITYORGAN 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 TOXICITYORGAN 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

ORGAN SYSTEM TOXICITYORGAN 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 TOXICITYORGAN SYSTEM TOXICITY

CARDIOVASCULAR

HYPOTENSION

Astragalus, Codonopsis, Prunella, Scrofularia, Salvia

HYPERTENSION

Ginseng

HYPERTENSION / CORONARY SPASM / PALPITATIONS

Ephedra

• ECHINACEAECHINACEA

Echinacea purpurea and angustifolia

ECHINACEAECHINACEA

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

GINGKOGINGKOGingko biloba

GINKGOGINKGO 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

GINKGOGINKGO 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 WortSt. John’s Wort

ST. JOHN’S WORTST. 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 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

GARLICAllium sativum

GARLICGARLICAllium sativum

GARLICGARLICAllium 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)

GARLICGARLICAllium 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 GINSENG Asian Panax ginseng

American Panax quinquefoliusSiberian Eleutherococcus senticosus

GINSENG GINSENG Asian Panax ginseng

American 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

GINSENG GINSENG Asian Panax ginseng

American 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)

GINSENGGINSENG Asian Panax ginseng

American 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

GOLDENSEAL Hydrasis canadensis

Golden SealGolden Seal

GOLDEN SEALGOLDEN 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 PalmettoSaw Palmetto

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-alpha-reductase activity

STUDIES

2 double blind studies showed significant improvement in objective and subjective data versus placebo and finasteride

SAWSAW PALMETTOPALMETTO Serenoa repens

TOXICITY

GI upset

DRUG INTERACTIONS

caution with hormonal therapies

VALERIAN Valeriana officinalis

VALERIANVALERIAN 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

VALERIANVALERIAN Valeriana officinalis

ANESTHETIC CONSIDERATIONS

Will likely potentiate barbiturate and benzodiazepine effects

(Should not be used with alcohol)

FEVERFEW Tanacetum parthenium

FeverfewFeverfew

FEVERFEWFEVERFEW Tanacetum 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

FEVERFEWFEVERFEW 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

GINGERZingiger oficinale

GINGERGINGERZingiger oficinale

USES

antinauseant

antispasmodic

MECHANISM

not stated for primary use

thromboxane synthetase inhibition

STUDIES

not found

GINGERGINGERZingiger 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 (MA HUANG)Ephedra sinica

USES

Diet aid

Bacteriostatic

Antitussive

MECHANISM

release of endogenous catecholamines (indirect sympathomimetic)

STUDIES

Not found

EPHEDRA (MA HUANG)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 ResourcesWorld Wide Web ResourcesOrganization Address Links

FDA http://www.fda.gov MEDWATCH

special nutritionals adverse event monitoring system

American http://www.herbs.org Herb Research

Botanical Foundation

Council

University of http://www.nnlm.nlm.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 ResourcesWorld 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