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Indian Journal of Anaesthesia 2007;51 (3) : 184-192 Indian Journal of Anaesthesia, June 2007 Special Article EFFECT OF COMMON HERBAL MEDICINES ON PATIENTS UNDERGOING ANAESTHESIA Yatindra Kumar Batra 1, Subramanyam Rajeev 2 Summary Herbal medicines are the oldest known remedies to mankind. Herbs have been used by all cultures throughout history but India has one of the oldest, and most diverse cultural living traditions associated with the use of medicinal plants. The use of these agents may h
  184 Indian Journal of Anaesthesia, June 2007 EFFECT OF COMMON HERBAL MEDICINES ONPATIENTS UNDERGOING ANAESTHESIA Yatindra Kumar Batra 1 , Subramanyam Rajeev 2 Summary  Herbal medicines are the oldest known remedies to mankind. Herbs have been used by all cultures throughout history but India has one of the oldest, and most diverse cultural living traditions associated with the use of medicinal plants. The use of these agents may have perioperative implications, which often is a result of various factors. The constituents of these medications may not be adequately described. Conventional agents like ste-roids, oral hypoglycaemic agent, nonsteroidal anti-inflammatory agents and antihistamines are frequently added to herbal medicines. Toxic materials like arsenic, mercury, lead, etc. have been detected from time to time insome herbs. The use of herbal medicines can result in drug interactions, most of which are less well defined.The interactions that are most important in the perioperative period include sympathomimetic, sedative, and coagulopathic effects. Less than 50% of patients admit to taking these medicines, which compounds the prob-lem. It is imperative that anaesthesiologists obtain a history of herbal medicine use from patients and anticipatethe adverse drug interactions. In case of any doubt, it may be prudent to stop these herbal medicines atleast 2-3 weeks prior to anaesthesia and surgery. Key words Herbal medicines; Anaesthesia; Complications, Drug interactions . Indian Journal of Anaesthesia 2007;51 (3) : 184-192   Special Article Introduction The oldest ‘prescriptions’ of hundreds of differentbotanicals and food in recorded history were found onBabylonian clay tablets and ancient Egyptian papyrus.Plants and herbals have been a part of many traditionalhealingpracticesthroughoutthehistoryofmankindinclud-ing: Chinese medicine, Ayurveda, a holistic system in thecivilization of India, Curanderismo, a Mexican Americanhealing tradition, as well as the practice of westernherbalism. Many botanical compounds were the basis of medical pharmacotherapeutics in the U.S. as recently asthe 1930’s. As the world witnessed an advancement of scientific methods there was demise in the practice of herbology 1. Thereemergingpopularityofnutraceuticalsandof herbal products in the late 1990’s led to the establish-ment of various schools for alternative medicine. Arecentstudy specifically designed to evaluate use of these medi-cations during the perioperative period demonstrated that22%ofthepreoperativepatientsreportuseofherbalmedi-cines and 51%, use of vitamins 2 .After all, thecontributionof botanicalscanseldombeoverlookedas30% ofallmod-ern conventional therapeutic agents are derived fromplants 3 . World Health Organization estimate revealed thatupto80%oftheworld’s populationstilldepends onherbalmedicines. Chronic ailments have made many patients at-tempt to cure their disease states with the use of self ad-ministered herbal medicines. Few of these conditions in-cludediabetesmellitus,malignancy,arthriticconditions,andAIDS. The inclusion of these nutraceuticals in the supple-ment category has made them easily available as over thecounter medicines 2 .Alternative medicine has been defined by The Na-tionalInstituteof Health asthefollowingsevenfields; alter-native systems (e.g. acupuncture, homeopathy and natur-opathy), bioelectromagnetism, diet and nutrition (e.g.macrobiotic diets), herbal remedies, manual healing meth-ods (e.g. chiropractic and massage therapy), mind/body in-terventions (e.g. meditation, hypnosis, biofeedback), andpharmacologic and biologic treatments (e.g.EDTAfor che-lationtherapy) 4 .Thisreviewislimitedtodiscussionofherbal 1. MD, FAMS (Professor), 2. MD, Senior Resident, Department of Anaesthesia and Intensive Care, Postgraduate Institute of Medical Educationand Research, Chandigarh-160012, India. Correspondence to: - Yatindra Kumar Batra, Professor, Department of Anaesthesia & Intensive Care,Post-graduate Institute of Medical Education & Research, Chandigarh 160012E mail: ykbatra@glide.net.in Accepted for publication on 20.4.07   185 remedies. The pharmacological effects and anaesthetic im-plicationsofsomeofthecommonlyusedherbsarediscussedand few others are mentioned in Table 1. Overview of commonly used traditionalIndian herbal medicines The use of herbal medicine srcinated in India longbackinpre-vedic period. Rigveda andAtharva-veda (5000years B.C.), theearliestdocumentedancient Indianknowl-edge have references on health and diseases. Texts likeCharak Samhita and Sushruta Samhita have documentedthis in about 1000 years B.C. Medicinal herbs have beenin use in one formor another, under indigenous systems of medicinelikeAyurveda,SidhaandUnani 5 . Morethan3000plants are recognized for their medicinal value, and are inuse in traditional, folk and herbal medicine, representingabout75%ofthemedicinalneeds oftheThirdWorldcoun-tries 6 . There are about 7000 firms manufacturing tradi-tional medicines with or without standardization in India,andhencenotmanyIndianproductsareavailableina stan-dard form 5 . Another problem of Indian herbal products isadulteration 7 . The common examples which are wellknown are substitution of the bark of  Holarrhenaantidysentrica by Wrightia tictoria , and Saraca indica by Trema orientalis 8 . The storage process of herbal medi-cines may not be adequate and may pose additional healthhazards. It has been reported that the stored drug samplesharbour mycotoxin-producingfungiin highfrequency.The Table 1 Commonly used herbs and theirperioperative implications Name of herb Uses Pharmacological Perioperative(Biological effects concernsname)Bilberry  Ophthalmic  Anthocyanidins  Increased risk  (Vaccinium problems boost production of perioperative uliginosum)  GI ailments of rhodopsin bleeding  Anti oxidant  Tannins have  Anti tumor- anti-inflamma-ogenic tory properties Black Cohosh  Gynaecological  Labour inducing  Hepatotoxic (Actaea disorders effects  Contraindicated  racemosa/   Musculoskel-  Hormonal effects in pregnancy Cimicifuga etal effects  Emmenagogue and lactation  racemosa) properties  Anovulatoryeffects Blue Cohosh  Gynaecological  More toxic than  Hepatotoxic ( Caulophyllum disorders black cohosh  Contraindicated  thalictroides ) in pregnancyand lactation Cranberry  Antibacterial  Inhibits metabo-  Increased risk of  (Vaccinium  Urinary tract lism of warfarin perioperative  oxycoccus) infection  Enhances immune bleedingsystem  Close INRmonitoring withwarfarin Ma Huang  Weight loss  Direct and  Discontinued 24 (Ephedra)  Mood enhancer indirect sympa- hr preop  Allergic rhinitis thomimmetic  Arrhythmias  Asthma actions  Haemodynamicinstability Green tea  Neurodegene-  Caffeine and  May antagonize (Camellia rative disease tannins cause actions of   sinensis)  Anti cancer stimulation of warfarin  Hypolipedemic CNS  May cause  Source of arrhythmiasvitamin K  Caution in renal  Antioxidant and thyroiddiseases  Insomnia Golden seal  Sore eyes  Potentially toxic  Fatal respiratory (  Hydrastis  GI problems alkaloids (hydra- failure Canadensis) stine and berb-  Interferes witherine) action of   Strongly inhibits heparin.CYP2D6 and  HypoglycemiaCYP3A4/5 Noni  Reduces blood  Anthraquinones  Hyperkalemia Indian sugar toxin  Acute hepatitis Mulberry  Hastens wound  Anti-nociceptive  Contraindicated (Morinda healing in effects in pregnancy  citrifolia) diabetics  Anti-inflammatory and lactationeffects Name of herb Uses Pharmacological Perioperative(Biological effects concernsname)Milk thistle  Lowers chol-  Antioxidant  Anaphylaxis (Silybum esterol levels  Antifibrinolytic  Skin reactions  marianum)  Reduces insulin activity  Neuropsych-resistance  Anti ological events  Anti cancer inflammatoryeffects  Immunomodul-ating effects Primrose  Autoimmune  Rich in aminoa-  Sedative (  Primula diseases cids and omega 6  May induce vulgaris)  Diabetic  Increases prost- seizures inneuropathy aglandins susceptible  Osteoporosis  Anti-inflam- patients  ARDS matory  Hypertension  Antithrombotic  Elevated serumlipids Saw palmetto  Benign prost-  Inhibits 5 alpha  May exacerbate (Serenoa atic hyperplasia reductase preexisting  repens) heart disease  Pancreatitis St John’s wort  Minor  Serotonin,  Decreased (Hypericum depression norepinephrine efficacy of other  perforatum) reuptake blocker drugs  Inhibits CYP  Serotoninsyndrome  Stopped 5 dayspreoperatively Yatindra Kumar Batra et al. Common herbal medicines and anaesthesia Contd.  186 Indian Journal of Anaesthesia, June 2007 harvestingpracticesandhightemperatureandmoisturecon-tentsareconducivetofungalinvasionandmycotoxinelabo-ration. Mycotoxins have been found in stored drugs like,roots/rhizomes of  Asparagus racemosus, Atropa bella-donna, Withania somnifera, Plumbago zelanica, fruitsof  Emblica officinalis, Terminalia chebula and seeds of   Macuna puriens 9 . Complete phytochemical investigationsofmost ofthemedicinallyimportant herbsof India havenotbeen carried out so far. Various contaminants both in theform of conventional drugs and heavy metals have beendetected in herbal preparations (Table 2).Herbal medicines are typically taken as teas, cap-sules, tablets, or extracts. But depending upon the typeand severity of symptoms, some preparations in China aregiven intravenously or subcutaneously. The mechanism of action of herbal medicine is not well-documented as towhether they act in a synergistic way or by additive ef-fects. Clinicalevaluationisalsodifficult, without knowingtheextenttowhichsynergyoccurswithintheherbalprepa-rations. Some components may function as potentiatorswithout having an intrinsic activity. St. John’s wort (  Hy- pericum perforatum , family Hypericaceae) is often re-garded as a good example of an herb with synergism andpolyvalent action and Ginger (  Zingiber officinale ) is an-other example of synergism. In general, the clinical trialdata on these preparations is in the embryonic stages,whereas the popularity of these compounds is fueled inpart by anecdotal evidence 10 . Arjuna (Terminaliaarjuna) Arjuna is grown in most parts of India and has beenused in ayurvedic formulations since ancient times. Be-sides its wide range of medicinal uses, Terminalia arjuna is also planted for shade and ornamental purposes. It hastherapeuticapplicationashypolipidemic, cardiacstimulant,hypotensive, cirrohsis of liver, diuretic, astringent,haemostatic,prostaglandinenhancing, coronaryriskmodu-lating properties, protection against NSAIDs induced gas-tric ulcer and against skin aliments like acne etc. Intraop-erative use of intravenous arjuna produced hypotension inanaesthetized dogs. Hypotension was blocked by propra-nolol but not by atropine or mepyramine maleate, indicat-ing mediation through beta receptors 11 . The product lit-erature states “Use of  Terminalia arjuna has not beenassociated with any severe adverse effects. However,comprehensive safety studies have not been performed.Safety in young children, pregnant or nursing women, orpeople with severe liver or kidney disease has not beenestablished”. Chamomile(  Matricariachamomilla) Chamomilehas beenusedhistoricallyfor GIdiscom-fort, peptic ulcer disease, paediatric colic, and mild anxi-ety. The mechanismof action may be through central ben-zodiazepine receptors. Several trials have noted hypnotic-sedative properties and reports of allergic reaction, how-ever no significant toxicity has been noted 12 . Mahuang (Ephedra) Ephedra, originallya nativeinChina is grownexten-sively in India. There are several Ephedra species used,including E equisetina, E sinica, E intermedia , and E geradiana . E. gerardiana in India is found in drier re-gions of temperate and alpine Himalaya from Kashmir toSikkim, Chamba, Lahul, Spiti and Ladakh 13 . Ephedra is abotanical source of ephedrine alkaloids, Indian ephedracontaining 0.28 to 2.79% by weight. Ephedrine was iso-latedfromephedra bytheJapanesechemistNagai, in1887.Ephedrine and pseudoephedrine are the most abundant Table 2 Common additives to herbal medicines Conventional drugs Heavy metalsCaffeine Aluminum Chlorpheniramine Arsenic Cyproheptadine Cadmium Dexamethasone Copper Diazepam Lead Diclofenac Mercury Dipyrone Tin Ephedrine Zink  FluocinonideHydrochlorothiazideIbuprofenIndomethacinMethyl testosteroneParacetamolPhenacetinPhenforminPhenylbutazonePrednisolonePromethazineTheophylline  187 Yatindra Kumar Batra et al. Common herbal medicines and anaesthesia constituents; other sympathomimetic alkaloids which arepresent in ephedra include methylephedrine, norephedrine,methylpseudoephedrine, and norpseudoephedrine. Themechanism of action of these alkaloids includes directagonism at  and  adrenergic receptors and indirectagonism by augmenting release of norepinephrine frompresynapticneurons. Clinically, this resultsintachycardia,hypertension, diaphoresis, bronchodilation, agitation, andmydriasis withretainedlightreflex 14 . Thealliedbenefits of Ephedraarenumerousincludingjointaches,lowbloodpres-sure, cold and flu symptoms, edema, enuresis, narcolepsy,asthma, and upper respiratory infections. It has gainedimmensepopularity for thebenefits in weight loss and as adrug to enhance sexual performance. It is a drug of abusewith euphoric, stimulant effects and street names like‘‘Herbal Ecstasy’’, ‘‘Cloud 9’’ and ‘‘Ultimate Xphoria’’.Currently, theuseofephedra isbannedbynumeroussport-ing associations. The adverse effects attributed to the con-sumptionof ephedra includenervousness, anxiety, palpita-tions, headaches, nausea, hypertension, seizures, strokes,myocardial infarction, hyperthermia, and death. Myocar-dialischemiaandinfarction,dysrhythmias,anduncontrolledhypertension have been reported. Chronic use may inducecardiomyopathy. Other adverse events have been reportedinclude palpitations, anxiety, vomiting, syncope, erythro-derma, insomnia, headache, psychosis and heat stroke.Ephedra is included in a growing list of herbal productsthat has beenassociated withhepatic injury 15 . Central ner-vous system involvement with vascular ischemia,haemorrhage, vasculitis and seizures has alsobeen associ-ated with its use 16 . Ephedra is one of the commonly usedherbs even by parturients 17 .Although the actual incidence of clinically importantsymptoms during the perioperative period associated withthe use of ephedra is not known, a signicant number of perioperativeeventsincludinghardtocontrolhypertension,causing myocardial infarction and stroke have been re-ported. Arrhythmias may be observed, particularly withhalothane, isoflurane, desflurane and digitalis. Tachyphy-laxis may be observed with intraoperative epinephrine 18 .Patients on chronic therapy tend to have exaggerated in-traoperative hypotension due to depletion of peripheralcatecholanie stores, which can be controlled with a directvasoconstrictor (eg, phenylephrine) instead of ephedrine.Concomitant usewith phenelzineor other monoamine oxi-daseinhibitorsmayresultininsomnia,headache,andtremu-lousness. Use with oxytocin has been shown to cause hy-pertension. Absolute contra-indications to products con-taining ephedra include ischemic heart disease, hyperten-sion, cerebrovascular disease, thyroid disease, diabetes,psychiatric disorders, prostamegaly and pregnancy or lac-tation. Theeliminationhalflifeof5.2hrindicatesthatephe-dra should be discontinued atleast 24 hr before surgery 19 . Ginger(  Zingiberoffcinale )(Adraka,Sunthi) GingerisinuseinIndiasincehistorictimesdatingataround400BC. Gingerhasbeendescribedasaneffectivetherapyfornausea, vomiting, motion sickness, hyperemesis gravidarum,PONV and vertigo. The mechanism to prevent nausea andvomiting includes actions at bothgut andbrain. 6-gingerols ingingercanenhancegastrointestinaltransportandgalanolactone,another active constituent, can act as a competitive antagonistat serotonin 5-HT3 receptors 18 . It is also used for respiratoryailments.Gingerhasbeenfoundtocausehyperglycaemia.Gin-ger is a potent inhibitor of thromboxane synthetase enzyme,whichcanprolongbleeding time 20 .The importance of the enzyme inhibition to theanaesthesiologist is that, use of ginger may alter bleedingtime, which therefore makes it imperative to avoid gingerin patients on anticoagulants like warfarin and heparin ordrugs such as NSAIDs and aspirin. This may also imposespecial concerns for regional anaesthesia in patients whoconsume ginger regularly 16 . Garlic (Allivum sativum) Garlic is one of the most popular herbs in the worldand is cultivated in most parts of India. It has been usedforseveralthousandyearstoflavour foodandbyAyurvedicphysicians for its medicinal properties. The most activeingredientofgarlicisallicin,whichcontainssulfurandwhencombined with breakdown products, gives garlic its char-acteristic smell. Crushing the garlic clove activates theenzyme allinase that converts alliin to allicin. Constituentsin garlic can block the cyclooxygenase pathway, prevent-ing the formation of inflammatory prostaglandins 21 .The beneficial effects are found to be in conditionslike infection, tumours, diabetes, hypertension,hyperlipidaemia and atherosclerosis. There is increasinginterest in its antihypertensive andantihypercholesterolaemicactivity. Garlic wasalsoadmin-istered to provide strength and to increase work capacity.Garlic is prescribed as a diuretic, expectorant, antimicro-
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