|Year : 2007 | Volume
| Issue : 3 | Page : 184-192
Effect of common herbal medicines on patients undergoing anaesthesia
Yatindra Kumar Batra1, Subramanyam Rajeev2
1 MD, FAMS (Professor), Department of Anaesthesia and Intensive Care, Postgraduate Institute of Medical Education and Research, Chandigarh-160012, India
2 MD, Senior Resident, Department of Anaesthesia and Intensive Care, Postgraduate Institute of Medical Education and Research, Chandigarh-160012, India
|Date of Acceptance||20-Apr-2007|
|Date of Web Publication||20-Mar-2010|
Yatindra Kumar Batra
Professor, Department of Anaesthesia & Intensive Care, Post-graduate Institute of Medical Education & Research, Chandigarh 160012
Source of Support: None, Conflict of Interest: None
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 steroids, 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 in some 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 problem. It is imperative that anaesthesiologists obtain a history of herbal medicine use from patients and anticipate the adverse drug interactions. In case of any doubt, it may be prudent to stop these herbal medicines atleast 23 weeks prior to anaesthesia and surgery.
Keywords: Herbal medicines; Anaesthesia; Complications, Drug interactions.
|How to cite this article:|
Batra YK, Rajeev S. Effect of common herbal medicines on patients undergoing anaesthesia. Indian J Anaesth 2007;51:184-92
| Introduction|| |
The oldest 'prescriptions' of hundreds of different botanicals and food in recorded history were found on Babylonian clay tablets and ancient Egyptian papyrus. Plants and herbals have been a part of many traditional healing practices throughout the history of mankind including: Chinese medicine, Ayurveda, a holistic system in the civilization of India, Curanderismo, a Mexican American healing tradition, as well as the practice of western herbalism. Many botanical compounds were the basis of medical pharmacotherapeutics in the U.S. as recently as the 1930's. As the world witnessed an advancement of scientific methods there was demise in the practice of herbology . The reemerging popularityof nutraceuticals and of herbal products in the late 1990's led to the establishment of various schools for alternative medicine. A recent study specifically designed to evaluate use of these medications during the perioperative period demonstrated that 22% of the preoperative patients report use of herbal medicines and 51%, use of vitamins . After all, the contribution of botanicals can seldom be overlooked as 30% of all modern conventional therapeutic agents are derived from plants . World Health Organization estimate revealed that up to 80% of the world's population still depends on herbal medicines. Chronic ailments have made many patients attempt to cure their disease states with the use of self administered herbal medicines. Few of these conditions include diabetes mellitus, malignancy, arthritic conditions, and AIDS. The inclusion of these nutraceuticals in the supplement category has made them easily available as over the counter medicines .
Alternative medicine has been defined by The National Institute of Health as the following seven fields; alternative systems (e.g. acupuncture, homeopathy and naturopathy), bioelectromagnetism, diet and nutrition (e.g. macrobiotic diets), herbal remedies, manual healing methods (e.g. chiropractic and massage therapy), mind/body interventions (e.g. meditation, hypnosis, biofeedback), and pharmacologic and biologic treatments (e.g.EDTA for chelation therapy) . This review islimitedtodiscussion of herbal remedies. The pharmacological effects and anaesthetic implications of some of the commonly used herbs are discussed and few others are mentioned in [Table 1].
| Overview of commonly used traditional Indian herbal medicines|| |
The use of herbal medicine originated in India long back in pre-vedic period. Rigveda andAtharva-veda (5000 years B.C.), the earliest documented ancient Indian knowledge have references on health and diseases. Texts like Charak Samhita and Sushruta Samhita have documented this in about 1000 years B.C. Medicinal herbs have been in use in one form or another, under indigenous systems of medicine likeAyurveda, Sidha and Unani . More than 3000 plants are recognized for their medicinal value, and are in use in traditional, folk and herbal medicine, representing about 75% of the medicinal needs of the Third World countries . There are about 7000 firms manufacturing traditional medicines with or without standardization in India, and hence not many Indian products are available in a standard form . Another problem of Indian herbal products is adulteration . The common examples which are well known are substitution of the bark of Holarrhena antidysentrica by Wrightia tictoria, and Saraca indica by Trema orientalis. The storage process of herbal medicines may not be adequate and may pose additional health hazards. It has been reported that the stored drug samples harbour mycotoxin-producing fungi in high frequency.The harvesting practices and high temperature and moisture contents are conducive to fungal invasion and mycotoxin elaboration. Mycotoxins have been found in stored drugs like, roots/rhizomes of Asparagus racemosus, Atropa belladonna, Withania somnifera, Plumbago zelanica, fruits of Emblica officinalis, Terminalia chebula and seeds of Macuna puriens. Complete phytochemical investigations of most of the medicinally important herbs of India have not been carried out so far. Various contaminants both in the form of conventional drugs and heavy metals have been detected in herbal preparations [Table 2].
Herbal medicines are typically taken as teas, capsules, tablets, or extracts. But depending upon the type and severity of symptoms, some preparations in China are given intravenously or subcutaneously. The mechanism of action of herbal medicine is not well-documented as to whether they act in a synergistic way or by additive effects. Clinical evaluation is also difficult, without knowing the extent to which synergy occurs within the herbal preparations. Some components may function as potentiators without having an intrinsic activity. St. John's wort (Hypericum perforatum, family Hypericaceae) is often regarded as a good example of an herb with synergism and polyvalent action and Ginger (Zingiber officinale) is another example of synergism. In general, the clinical trial data on these preparations is in the embryonic stages, whereas the popularity of these compounds is fueled in part by anecdotal evidence .
Arjuna (Terminalia arjuna)
Arjuna is grown in most parts of India and has been used in ayurvedic formulations since ancient times. Besides its wide range of medicinal uses, Terminalia arjuna is also planted for shade and ornamental purposes. It has therapeutic application as hypolipidemic, cardiac stimulant, hypotensive, cirrohsis of liver, diuretic, astringent, haemostatic, prostaglandin enhancing, coronary risk modulating properties, protection against NSAIDs induced gastric ulcer and against skin aliments like acne etc. Intraoperative use of intravenous arjuna produced hypotension in anaesthetized dogs. Hypotension was blocked by propranolol but not by atropine or mepyramine maleate, indicating mediation through beta receptors . The product literature states "Use of Terminalia arjuna has not been associated with any severe adverse effects. However, comprehensive safety studies have not been performed. Safety in young children, pregnant or nursing women, or people with severe liver or kidney disease has not been established".
Chamomile (Matricaria chamomilla)
Chamomile has been used historically for GI discomfort, peptic ulcer disease, paediatric colic, and mild anxiety. The mechanism of action may be through central benzodiazepine receptors. Several trials have noted hypnotic-sedative properties and reports of allergic reaction, however no significant toxicity has been noted .
Ma huang (Ephedra)
Ephedra, originally a native in China is grown extensively 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 regions of temperate and alpine Himalaya from Kashmir to Sikkim, Chamba, Lahul, Spiti and Ladakh . Ephedra is a botanical source of ephedrine alkaloids, Indian ephedra containing 0.28 to 2.79% by weight. Ephedrine was isolated from ephedra by the Japanese chemist Nagai, in 1887. Ephedrine and pseudoephedrine are the most abundant constituents; other sympathomimetic alkaloids which are present in ephedra include methylephedrine, norephedrine, methylpseudoephedrine, and norpseudoephedrine. The mechanism of action of these alkaloids includes direct agonism atá andâ adrenergic receptors and indirect agonism by augmenting release of norepinephrine from presynaptic neurons. Clinically, this results in tachycardia, hypertension, diaphoresis, bronchodilation, agitation, and mydriasis with retained light reflex . The allied benefits of Ephedra are numerous including joint aches, low blood pressure, cold and flu symptoms, edema, enuresis, narcolepsy, asthma, and upper respiratory infections. It has gained immense popularity for the benefits in weight loss and as a drug to enhance sexual performance. It is a drug of abuse with euphoric, stimulant effects and street names like ''Herbal Ecstasy'', ''Cloud 9'' and ''Ultimate Xphoria''. Currently, the use of ephedra is banned by numerous sporting associations. The adverse effects attributed to the consumption of ephedra include nervousness, anxiety, palpitations, headaches, nausea, hypertension, seizures, strokes, myocardial infarction, hyperthermia, and death. Myocardial ischemia and infarction, dysrhythmias, and uncontrolled hypertension have been reported. Chronic use may induce cardiomyopathy. Other adverse events have been reported include palpitations, anxiety, vomiting, syncope, erythroderma, insomnia, headache, psychosis and heat stroke. Ephedra is included in a growing list of herbal products that has been associated with hepatic injury . Central nervous system involvement with vascular ischemia, haemorrhage, vasculitis and seizures has also been associated with its use . Ephedra is one of the commonly used herbs even by parturients .
Although the actual incidence of clinically important symptoms during the perioperative period associated with the use of ephedra is not known, a signicant number of perioperative events including hard to control hypertension, causing myocardial infarction and stroke have been reported. Arrhythmias may be observed, particularly with halothane, isoflurane, desflurane and digitalis. Tachyphylaxis may be observed with intraoperative epinephrine . Patients on chronic therapy tend to have exaggerated intraoperative hypotension due to depletion of peripheral catecholanie stores, which can be controlled with a direct vasoconstrictor (eg, phenylephrine) instead of ephedrine. Concomitant use with phenelzine or other monoamine oxidase inhibitors may result in insomnia, headache, and tremulousness. Use with oxytocin has been shown to cause hypertension. Absolute contraindications to products containing ephedra include ischemic heart disease, hypertension, cerebrovascular disease, thyroid disease, diabetes, psychiatric disorders, prostamegaly and pregnancy or lactation. The elimination half life of 5.2 hr indicates that ephedra should be discontinued atleast 24 hr before surgery .
Ginger (Zingiber offcinale)(Adraka, Sunthi)
Ginger is in use in India since historic times dating at around 400 BC. Ginger has been described as an effective therapy for nausea, vomiting, motion sickness, hyperemesis gravidarum, PONV and vertigo. The mechanism to prevent nausea and vomiting includes actions at both gut and brain. 6-gingerols in ginger can enhance gastro-intestinal transport and galanolactone, another active constituent, can act as a competitive antagonist at serotonin 5-HT3 receptors . It is also used for respiratory ailments. Ginger has been found to cause hyperglycaemia. Ginger is a potent inhibitor of thromboxane synthetase enzyme, which can prolong bleeding time .
The importance of the enzyme inhibition to the anaesthesiologist is that, use of ginger may alter bleeding time, which therefore makes it imperative to avoid ginger in patients on anticoagulants like warfarin and heparin or drugs such as NSAIDs and aspirin. This may also impose special concerns for regional anaesthesia in patients who consume ginger regularly .
Garlic (Allivum sativum)
Garlic is one of the most popular herbs in the world and is cultivated in most parts of India. It has been used for several thousand years to flavour food and by Ayurvedic physicians for its medicinal properties. The most active ingredient of garlic is allicin, which contains sulfur and when combined with breakdown products, gives garlic its characteristic smell. Crushing the garlic clove activates the enzyme allinase that converts alliin to allicin. Constituents in garlic can block the cyclooxygenase pathway, preventing the formation of inflammatory prostaglandins .
The beneficial effects are found to be in conditions like infection, tumours, diabetes, hypertension, hyperlipidaemia and atherosclerosis. There is increasing interest in its antihypertensive and antihypercholesterolaemic activity. Garlic was also administered to provide strength and to increase work capacity. Garlic is prescribed as a diuretic, expectorant, antimicrobial, and antidiarrhoeal agent. The adverse effects of garlic include nausea (6%), hypotension (1.3%) and allergy(1.1%) .
The use of garlic may have anaesthetic implications by augmenting the effects of warfarin, heparin, nonsteriodal anti-inflammatory drugs (NSAIDs), and aspirin, and may result in an abnormal bleeding time, which can lead to an increased risk for intra-operative or postoperative bleeding. This may also cause concerns for neuraxial anaesthesia. Pharmacokinetic data are unavailable, however, owing to the antiplatelet effect; garlic is discontinued atleast 7 days before surgery .
Maidenhair tree (Ginkgo biloba)
Ginkgo biloba is grown for its ornamental purpose and as a source of herbal medicine. Ginkgo extract contains several flavonoids, terpenoids and organic acids that are believed to protect vascular walls and nerve cells by acting as free radicals and by inhibiting platelet activating factors. It can decrease erythrocyte aggregation and blood viscosity. Ginkgo (120 mg.day -1 ) is used to treat cognitive deficits such as Alzheimer's disease, multi-infarct dementia, asthma, angina, intermittent claudication, sexual dysfunction and eye ailments. It is also used in peripheral vascular disease due to its property of decreasing blood viscosity and increasing flow. Chinese herbalists use this drug for respiratory infections . The adverse effects of ginkgo are limited to mild gastrointestinal upset and headache. Various ginkgolides, have platelet activating factor (PAF) antagonist properties and mediate the antiplatelet and anti-inflammatory properties. There are several reports of intracranial haemorrhage in patients using ginkgo. In a case report, a healthy 34 yr old man bled unexpectedly (Hb 16.5 to 5.4 g.dl -1 ) following laparoscopic cholecystectomy, and on further questioning it was found that he was consuming 2 tablets/day of ginkgo . In spite of the cognition enhancing properties, this herb is neurotoxic.
Ginkgo biloba is associated with an increased risk of perioperative bleeding due to interactions with aspirin, or any NSAIDs and anticoagulants such as warfarin and heparin, and their coadministration is hence not recommended. Seizures may be precipitated due to reduced efficacy of anticonvulsants, and the risk may be further exaggerated with concomitant tricyclic antidepressants .
Ginseng (Panax ginseng)
Ginseng is the most expensive and one of the most widely used herbal drugs throughout the world. There are three main subspecies of ginseng: Panax ginseng, Panax quinquefolius and Panax pseudoginseng. Active compound in panax ginseng is Ginsenoside. Ginseng has mild sympathomimetic activity and may interact with monoamine oxidase inhibitors . This herb is well known since ancient times, as an aphrodisiac, anti-aging, and energy enhancing tonic. It is a drug of abuse by athletes who consume this to boost their ''energy levels''. Other effects include augmentation of adrenal steroidogenesis and immunomodulation. Ginseng is consumed as a raw herb, powder, or made into ginseng tea . Adverse effects may include irritability, insomnia, and GI disturbance in addition to hypoglycaemia, hypertension, nervousness, insomnia and skin rashes. Weak estrogenic potential may predispose to gynaecomastia and vaginal bleeding . It may predispose to perioperative bleeding by inhibiting platelet aggregation and prolonging activated partial thromboplastin time, probably due to vitamin K antagonism. It may also predispose to hypoglycaemia. Ginseng may interact with oral anticoagulants, antiplatelet agents, corticosteroids, and hypoglycaemic agents .
The use of Ginseng may thus have perioperative implications and should be avoided in patients on anticoagulant medications such as warfarin, heparin, NSAIDs and aspirin. The presence of hypertension and its effects like, the occurence of target organ damage, volume depletion, autonomic instability due to long standing disease may be of additional perioperative concern. Monitoring blood glucose is imperative particularly in diabetic patients on oral hypoglycaemic agents or insulin, due to the risk of hypoglycaemia that may be caused with ginseng. Maniac episodes may be precipitated with concomitant MAOI . It is one of the popular herbs even among parturients. The antiplatelet effect may cause concerns with neuraxial blockades commonly employed in parturients. Ginseng should be avoided in pregnancy, in children, lactating women, and in patients with cardiovascular disease .
Grapefruit juice, is a popular beverage, that may decrease atherosclerotic plaque formation and inhibit cancer cell proliferation. Unlike other citrus fruits this can inhibit CYP3A4 and can alter metabolism of various medications .
Kava kava (Piper methysticum)
Kava was originally in use in South Pacific, as their ceremonial drink, and is now used for its medicinal values in other parts of the world as well. It is used as an alternative to sedatives and anxiolytics. Kavalactones (also called kava pyrones), the active component of kava, may work by binding to g-aminobutyric acid (GABA) receptor inhibitors. It is used to treat gonorrhea and many skin diseases. In large doses, kava can lead to ''kava dermopathy,'' which causes flaking and a yellowing of the skin. Several studies report extra pyramidal-like dystonic reactions and visual disturbances with use of kava. Use of kava with alcohol or other sedatives is contraindicated, as is use in pregnancy and lactation . Hepatotoxicity has been recently reported .
The use of kava may potentiate the effects of benzodiazepines and barbiturates are potentiated. Ethanol can increase the hypnotic effects of kava kava .
St. John's wort (Hypericum perforatum)
St. John's wort has been used medically since the day of Hippocrates. The therapeutic effects and toxicity of the herb have been implicated to two extensively studied compounds hypericin and hyperforin, which are rich in ripe fruits 15. Though traditionally used for mild to moderate depression, it does not have any role in the treatment of major depression. It has found a place in the treatment of various other ailments: anxiety, insomnia, irritability, neurosis, migraines, dyspepsia, gastritis, inflammatory bowel disease, sciatica, pain associated with herpes zoster, trigeminal and other chronic neuralgia, myalgia, and dental extraction. In addition it is used topically in various dermatological conditions. The herb is available in tablet, capsule, or tea form as well as a cream, oil, or liquid tincture . The most widely accepted premise to describe the molecular basis of its action is on biogenic amine hypothesis. The predominant mechanism of action is serotonin reuptake inhibition, other mechanisms include monoamine oxidase inhibition, interference with melatonin secretion, and uptake of norepinephrine . The electroencephalographic changes seen in patients taking St John's Wort though similar to patients on selective serotonin reuptake inhibitors, the proposed mechanism is different from SSRIs . Hypericum extracts suppress the hypothalamic pituitary axis and reduce corticotrophin releasing hormone and interleukin 6 release, thus mitigating depressive symptoms . In addition effects on GABA receptors, cholinergic receptors, inhibition of viral activity, anti inflammatory activity and anti cancer benefits are under investigation. St John's wort has been shown to induce cytochrome P450 system, particularly CYP 3A4 leading to altered metabolism of co-administered drugs. It can increase the metabolism of drugs like alfentanil, midazolam, lidocaine, calcium channel blockers, indinavir, estradiol, digoxin, oral contraceptives warfarin, theophylline, oral anticoagulants and cyclosporine . Serotonin syndrome may be precipitated when St. John's wort is used with conventional antidepressants, necessitating precautionary measures similar to those for patients taking conventional MAO inhibitors. Discontinuing St John's wort after protracted use may lead to a rebound increase in plasma concentrations of these drugs . Side effects described include dry mouth, dizziness, fatigue, constipation, and nausea. The most prominent adverse effect is photosensitivity, attributed to its hypericin component. Although there have been no reports of adverse effects on cardiac conduction, concomitant use of SSRIs may precipitate serotonergic syndrome, characterized by tremors, hypertonicity, myoclonus, autonomic dysfunction, hallucinosis, hyperthermia, and even death . Other less common adverse effects include sexual dysfunction, hair loss, elevated thyroid-stimulating hormone, psychotoxic reactions, and reports of hypertension and hypertensive crisis. Seizures have been noted in animals, but there are no human case reports of this. Withdrawal symptoms may be observed after stopping the drug following a high dose therapy. There is no data till date on the treatment of toxicity . The use of this herb is popular even among parturients and children.
The anaesthesiologist should preoperatively review additional medications or herbs that the patient may be taking. Delayed emergence from anaesthesia (fentanyl, propofol and sevoflurane) and cardiovascular collapse has been reported . Concomitant use of sympathomimetic amines, MAOIs and tyramine containing foods (cheese, beer, wine) is not advisable to prevent the occurrence of serotonin syndrome. The drug interactions make it imperative to discontinue St John's Wort preoperatively in patients awaiting transplant due to the risk of rejection. Patients on warfarin may be at risk for thrombotic complications because typical doses of warfarin may not provide adequate protection. The pharmacokinetic data described in humans with a median elimination half life of 43.1 hr for hypericin suggest that this drug should be discontinued at least 5 days preoperatively . In parturients, the main interactions are with pethidine, used for labor analgesia where it could result in hyperthermia, hypertension, hypotension, rigidity, seizures, and coma. In addition, ephedrine commonly used to treat spinal hypotension, may have an accentuated response because of more neurotransmitter available for release. As St John's Wort increases uterine tone in animal studies, it is contraindicated in pregnancy. Safety data during lactation is sparse, though mothers have complained of drowsiness or lethargy in newborns exposed to St John's Wort .
Valerian root (Valeriana officinalis)
Valerian root has been used for centuries as a sedative agent and sleep aid. Similar to kava, action on GABA receptors may be responsible for the sedative effect. Recently, it has been used mainly for other ailments like insomnia, jet lag, migraine headaches, fatigue, and intestinal cramps. Side effects may include headache, excitability, uneasiness, and cardiac disturbances. The use of this drug is not popular among parturients with only about 0.4% consuming this herb. There are reports of liver dysfunction and these are considered to be idiosyncratic reactions .
Valerian root potentiates sedative effects of anaesthetic agents. Sudden abstinence may precipitate withdrawal-type syndrome .
| Conclusion|| |
Understanding the ingredients and constituents of herbal medicine associated with the use of herbal medicines is important to anaesthesiologists involved in patient care. Asking patients about self-care and treatments used outside the hospital is an important part of the patient history. Herbal therapies are very popular for various conditions despite the lack of strong research supporting some of their use. In spite of high degree of interrater observer unreliability, patients are likely to seek to herbal medicines as a means of self-treatment and a way to maintain additional life control . It is vital for the anaesthesiologist to have knowledge of the various interactions associated with the use of herbal medicines [Table 3]. Many of these agents lead to an increased risk of perioperative bleeding, and toxicity on almost all the systems has been reported [Table 4]. When contemplating this extremely complex subject, it is important to remember that 'Natural' does not necessarily mean safe. It is imperative to remember that at this time, much of the available information is anecdotal and future double-blind, placebo-controlled trials are needed. Active ingredients are not consistent between studies making it difficult to extrapolate meaningful data. Patients should be encouraged to discontinue these products well in advance based on the pharmacokinetic data or when in doubt two to three weeks prior to surgery .
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[Table 1], [Table 2], [Table 3], [Table 4]