Herbal Supplements and Anesthesia

Introduction

• The use of herbal supplements by patients is widespread in the United States, with reported use ranging from 12% to 32%.¹ This poses a challenge to anesthesiologists and surgeons encountering these patients in the perioperative setting, where patients have an increased risk of adverse reactions due to polypharmacy and physiological stressors.
• Due to the classification of herbal medications as dietary supplements by the Food and Drug Administration in the United States, they are exempt from the safety and efficacy requirements that apply to prescription or over-the-counter medications. Consequently, despite the wide range of supplements available in the market, few have been carefully studied with delineated pharmacologic pathways.
• Attributable side effects from herbal supplements are broad-ranging, including coagulation disorders, hepatotoxicity, and cardiovascular instability.²

Common Herbal Supplements and Anesthetic Considerations

Echinacea

• Echinacea is commonly used for the prophylaxis and treatment of upper respiratory infections and is believed to have immunostimulatory activity against viral, bacterial, and fungal infections. In vitro and animal studies have shown that echinacea extracts modulate the body’s cytokine levels, enhance macrophage phagocytosis, and activate natural killer cells.
• Echinacea is associated with known side effects, including allergic reactions, headaches, dizziness, and gastrointestinal disturbances. Chronic echinacea use can cause hepatoxicity, so the concomitant use of hepatotoxic drugs can potentially cause hepatic injury. Additionally, the immunostimulatory effects of echinacea pose a potential risk of diminishing the effectiveness of immunosuppressant medications used for organ transplantation.^3,4
• The Society for Perioperative Assessment and Quality Improvement (SPAQI) recommends discontinuing 1-2 weeks prior to surgery.^5,6

Ephedra

• Ephedra, also known as Ma Huang, is commonly used as an appetite suppressant, central nervous system (CNS) stimulant, and for the management of asthma. Its effects are directly attributed to the alkaloids containing ephedrine, pseudoephedrine, methylephedrine, and norpseudoephedrine.^3,4
• Side effects of ephedra are directly related to its nonselective alpha- and beta-receptor agonism. These include hypertension, tachycardia, cardiac arrhythmias, seizures, and stroke. Chronic use may cause cardiomyopathy. Under anesthesia, ephedra may interact with other sympathomimetic drugs, resulting in life-threatening arrhythmias and cardiovascular instability. Its use has been restricted in both the United States and Australia.^3,4
• Due to its restricted use in the United States and broad-ranging effects, SPAQI recommends discontinuing the use of ephedra altogether.⁶

Garlic

• Garlic is widely used in cooking and is thought to be beneficial for atherosclerosis, hypertension, hyperlipidemia, and even certain types of tumors. Its medicinal properties are attributed to cysteine, which decreases thromboxane formation and alters arachidonic acid metabolism.^4,7
• Garlic also inhibits platelet formation in a dose-dependent fashion. It appears to potentiate other platelet inhibitors such as prostacyclin, forskolin, indomethacin, and dipyridamole, and its inhibitory effects appear to be irreversible. Due to their platelet effects, SPAQI recommends discontinuing garlic for 2 weeks prior to surgery.⁶

Ginger

• Ginger is believed to have anti-inflammatory and antiemetic properties and has been investigated as a supplement to reduce the risk of postoperative nausea and vomiting (PONV). It is thought to directly stimulate the gastrointestinal tract and inhibit peripheral and central serotonergic pathways. However, a systematic review found no difference between the use of ginger and a placebo for PONV, and therefore, it is not regularly recommended for use in the perioperative setting.⁸
• Ginger is also a potent inhibitor of the thromboxane synthetase enzyme, which can prolong bleeding time in patients. SPAQI recommends discontinuing ginger for 2 weeks prior to surgery.⁶

Ginkgo Biloba

• Ginkgo biloba has been used to treat cognitive disorders, multi-infant dementia, and peripheral vascular disease. Studies have shown that ginkgo appears to stabilize or improve cognition in dementia. The pharmacologic effects of ginkgo have been attributed to its flavonoids, terpenoids, and organic acids. Ginkgo appears to modulate vasoregulation, act as an antioxidant, and inhibit platelet-activating factor.^4,8
• Due to the potential interactions with anticoagulant medications as well as its platelet inhibitory effects, ginkgo has the potential to increase postoperative bleeding, and SPAQI recommends discontinuing ginkgo biloba 2 weeks prior to surgery.⁶

Ginseng

• Ginseng is frequently used in traditional Chinese medicine and has been attributed to have stimulant and mood-enhancing properties, as well as immunomodulatory effects. It has also been shown to improve glucose sensitivity and insulin response in patients with diabetes. However, due to the wide-ranging effects of the herb, the exact pharmacological effects and interactions of ginseng are not well understood.
• Ginseng appears to have a mild sympathomimetic effect due to its interaction with monoamine oxidase (MAO). It also appears to have sodium channel inhibition effects on the CNS, which provides some neuroprotective effects. When taken in large quantities, some have reported adverse effects such as irritability and insomnia, potentially due to its sympathomimetic effects. Additionally, concurrent use of ginseng and MAO inhibitors may result in adverse neurologic effects.^4,5,8
• Ginseng also has irreversible platelet inhibition effects in vitro and may cause an increased risk of bleeding postoperatively. SPAQI recommends discontinuing ginseng for 2 weeks prior to surgery.⁶

Fish Oil

• Fish oil supplementation provides a concentrated source of long-chain omega-3 fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are thought to be beneficial for cardiovascular health, lower triglyceride levels, and improve endothelial vasodilation. However, both EPA and DHA may compete with arachidonic acid, resulting in reduced production of prothrombotic metabolites and reduced platelet aggregation.
• There is a possible risk of increased bleeding due to platelet inhibition by fish oil. However, current evidence does not show a substantial impact on bleeding.⁹ SPAQI recommends continuing fish oils through the perioperative period.⁶

Kava

• Kava is a CNS depressant and is used as an anxiolytic and a sedative. It has a gamma-aminobutyric acid (GABA) potentiation effect, and tolerance develops after long-term use.^3,4,6,7
• It potentiates the inhibitory neurotransmission effects of anesthetics such as opiates, benzodiazepines, and barbiturates. Other side effects include hepatotoxicity, extrapyramidal-like dystonic reactions, and dermatologic changes.^3,4,6
• SPAQI recommends discontinuing kava for 2 weeks prior to surgery.⁶

Saw Palmetto

• Saw palmetto is used for the treatment of benign prostatic hyperplasia. It is found to increase bleeding time, though the mechanism of action is not known. In rodents, it is found to inhibit cyclooxygenase and cause platelet dysfunction.
• SPAQI recommends discontinuing for 2 weeks prior to surgery.⁶

St. John’s Wort

• St. John’s wort is a widely used supplement for mood disorders and mild depression. Its pharmacological effects are similar to those of MAO inhibitors, reducing the reuptake of serotonin, norepinephrine, and dopamine by neurons. Due to its effects on neurotransmitters, it has a high potential for interaction with serotonergic drugs prevalent in anesthesia, as well as other antidepressant medications.
• The use of St. John’s wort and serotonergic medications may cause muscle rigidity, autonomic dysfunction, and altered mental status. St. John’s wort also has sedative effects, which may prolong the effects of anesthesia.
• Additionally, St. John’s wort is a potent inducer of the hepatic P450 CYP3A4, which may increase the metabolism of many drugs reliant on the hepatic cytochrome. Common drugs affected are midazolam, alfentanil, lidocaine, and some antirejection medications. It is also an inhibitor of P450 2C9, which reduces the effects of warfarin and nonsteroidal anti-inflammatory drugs.^4,5,6,10
• SPAQI recommends discontinuing St. John’s Wort for 2 weeks prior to surgery. This is especially important for patients who are awaiting organ transplantation or require anticoagulation postoperatively.⁶

Valerian

• Valerian is most commonly used for the treatment of insomnia, but is also used as an anxiolytic and a CNS depressant. It has a dose-dependent effect on the modulation of GABA-mediated neurotransmitters and is thought to reduce GABA breakdown and reuptake.
• It has a high risk of interacting with anesthesia medications, especially with medications that act similarly on GABA neurotransmitters. Patients taking valerian may experience prolonged effects of opiates, benzodiazepines, and barbiturates.
• Valerian may cause physical dependence after prolonged use. Abrupt discontinuation of valerian may result in benzodiazepine-like withdrawal. Literature on valerian during the perioperative period is mixed. While some recommend tapering, SPAQI recommends continuing during the perioperative period.^4,5,6

Summary

• SPAQI recommends explicit preoperative inquiry about herbal supplement use, as many patients do not disclose this information.⁶
• The 2-week discontinuation interval is a consensus recommendation to minimize perioperative risks, particularly for supplements affecting coagulation, cardiovascular stability, or CNS depression.^4,6,7,8,10
• Data on exact discontinuation intervals for some supplements are limited; recommendations err on the side of caution.^4,6,7,8,10