Echinacea

Three species of Echinacea , a member of the daisy family, are used for the prophylaxis and treatment of viral (decreasing the incidence and duration of the common cold), bacterial, and fungal infections, particularly those of upper respiratory origin, although its efficacy in fungal infections is doubtful. The biological activity of Echinacea could be immunostimulatory, immunosuppressive, or antiinflammatory. Although studies have not specifically addressed interactions between Echinacea and immunosuppressive drugs, experts generally warn against the concomitant use of Echinacea and these drugs because of the probability of diminished effectiveness. In contrast to its immunostimulatory effects with short-term use, long-term use of more than 8 weeks is accompanied by the potential for immunosuppression and a theoretically increased risk for postsurgical poor wound healing and opportunistic infections. A recent phytochemical study identified a potential immunosuppressant compound from Echinacea —cynarine.

Information about Echinacea’s pharmacokinetics is still limited. Echinacea significantly reduced plasma concentrations of S-warfarin, but did not significantly affect warfarin pharmacodynamics and platelet aggregation in healthy subjects. However, this herb should be discontinued as far in advance of surgery as possible when compromises in hepatic function or blood flow are anticipated. In the absence of definitive information, patients with preexisting liver dysfunction should be cautious in using Echinacea .

Ephedra

Ephedra, known as ma huang in Chinese medicine, is a shrub native to central Asia. It is used to promote weight loss, increase energy, and treat respiratory conditions such as asthma and bronchitis. Ephedra contains alkaloids, including ephedrine, pseudoephedrine, norephedrine, methylephedrine, and norpseudoephedrine. Commercial preparations can be standardized to a fixed ephedrine content. Publicity about adverse reactions to this herb prompted the FDA to bar its sale in 2004, but ephedra is still widely available via the Internet.

Ephedra causes dose-dependent increases in arterial blood pressure and heart rate. Ephedrine, the predominant active compound, is a noncatecholamine sympathomimetic that exhibits α ₁ , β ₁ , and β ₂ activity indirectly by releasing endogenous norepinephrine (noradrenaline). These sympathomimetic effects have been associated with more than 1070 reported adverse events, including fatal cardiac and central nervous system complications. Vasoconstriction and, in some cases, vasospasm of coronary and cerebral arteries can cause myocardial infarction and thrombotic stroke. Ephedra can also affect cardiovascular function by causing hypersensitivity myocarditis, characterized by cardiomyopathy with myocardial lymphocyte and eosinophil infiltration. Long-term use results in tachyphylaxis from depletion of endogenous catecholamine stores and can contribute to perioperative hemodynamic instability. In these situations, direct-acting sympathomimetics may be preferred as first-line therapy for intraoperative hypotension and bradycardia. Concomitant use of ephedra and monoamine oxidase inhibitors can result in life-threatening hyperpyrexia, hypertension, and coma. Finally, continuous ephedra is a rare cause of radiolucent kidney stones. Recently, there was a case report describing acute angle-closure glaucoma caused by ephedra.

The pharmacokinetics of ephedrine have been studied in humans. Ephedrine has an elimination half-life of 5.2 hours, with 70% to 80% of the compound excreted unchanged in urine. Based on the pharmacokinetic data and the known cardiovascular risks associated with ephedra, including myocardial infarction, stroke, and cardiovascular collapse from catecholamine depletion, this herb should be discontinued at least 24 hours before surgery.

Garlic

Garlic is one of the most extensively researched medicinal plants. It has the potential to modify the risk for atherosclerosis by reducing arterial blood pressure, thrombus formation, and serum lipid and cholesterol concentrations. These effects are primarily attributed to its sulfur-containing compounds, particularly allicin and its transformation products. Commercial garlic preparations can be standardized to a fixed alliin and allicin content.

Garlic inhibits platelet aggregation in vivo in a concentration-dependent fashion. The effect of one of its constituents, ajoene, is irreversible and can enhance the effect of other platelet inhibitors such as prostacyclin, forskolin, indomethacin, and dipyridamole. Although the effects are not consistently demonstrated in volunteers, there is one case described in an 80 year old who had a spontaneous epidural hematoma develop that was attributed to continuous garlic use. Garlic has interacted with warfarin, resulting in an increased international normalized ratio (INR).

In addition to bleeding concerns, garlic can decrease systemic and pulmonary vascular resistance in laboratory animals, but this effect is marginal in humans. Although there are insufficient pharmacokinetic data on garlic’s constituents, the potential for irreversible inhibition of platelet function may warrant discontinuation of garlic at least 7 days before surgery, especially if postoperative bleeding is a particular concern or other anticoagulants are given. Additionally, garlic’s pharmacokinetics should be considered when a risk-benefit analysis is made for neuraxial techniques.

Ginger

Ginger ( Zingiber officinale ) is a popular spice with a long history of use in Chinese, Indian, Arabic, and Greco-Roman herbal medicines. Ginger has a wide range of reported health benefits for those with arthritis, rheumatism, sprains, muscular aches, pains, sore throats, cramps, constipation, indigestion, nausea, vomiting, hypertension, dementia, fever, infectious diseases, and helminthiasis. Ginger contains up to 3% volatile oil, mostly monoterpenoids and sesquiterpenoids. Gingerols are representative compounds in ginger.

Ginger is an antiemetic and has been used to treat motion sickness and to prevent nausea after laparoscopy. The number of postoperative antiemetic medications was significantly reduced after aromatherapy with essential oil of ginger. In another recent trial, ginger supplementation reduced the severity of acute chemotherapy-induced nausea in adult cancer patients and compared favorably to conventional antiemetics.

In an in vitro study, gingerols and related analogues inhibited arachidonic acid–induced human platelet serotonin release and aggregation, with a potency similar to that of aspirin. In another in vitro study, the antiplatelet effects of 20 ginger constituents were evaluated. Five constituents showed antiplatelet activities at relatively low concentrations. One of the ginger compounds (8-paradol) was the most potent cyclooxygenase-1 inhibitor and antiplatelet aggregation drug. In a case report, a ginger-phenprocoumon combination resulted in an increased INR and epistaxis. Although the sample size was relatively small, the platelet inhibition potential of ginger has been suggested in a pilot clinical study. This result may warrant the discontinuation of ginger at least 2 weeks before surgery,

Ginkgo

Ginkgo is derived from the leaf of G. biloba and has been used for cognitive disorders, peripheral vascular disease, age-related macular degeneration, vertigo, tinnitus, erectile dysfunction, and altitude sickness. Studies have suggested that ginkgo can stabilize or improve cognitive performance in patients with Alzheimer disease and multiinfarct dementia, but not in healthy geriatric patients. The compounds that might be responsible for its pharmacologic effects are the terpenoids and flavonoids. The two ginkgo extracts used in clinical trials are standardized to ginkgo-flavone glycosides and terpenoids.

Ginkgo alters vasoregulation, acts as an antioxidant, modulates neurotransmitter and receptor activity, and inhibits platelet-activating factor. Of these effects, inhibition of platelet-activating factor is of primary concern for the perioperative period. Although bleeding complications have not occurred in clinical trials, four cases of spontaneous intracranial bleeding, one case of spontaneous hyphema, and one case of postoperative bleeding after laparoscopic cholecystectomy have been described when ginkgo was being taken.

Terpene trilactones are highly bioavailable when administered orally. The elimination half-lives of the terpene trilactones after oral administration are between 3 and 10 hours. For ginkgolide B, a dosage of 40 mg twice daily resulted in a higher area under the curve, and a longer half-life and residence time, than after a single 80-mg dose. A once daily dose of 80 mg guaranteed a larger maximum concentration peak (T _max ) that was reached 2 to 3 hours after administration. The pharmacokinetics of terpene trilactones in three different ginkgo preparations in human plasma indicate that ginkgo should be discontinued at least 2 weeks before surgery to avoid bleeding.

Ginseng

Among the several species of ginseng used for their pharmacologic effects, Asian ginseng (Panax ginseng) and American ginseng (Panax quinquefolius) are the most commonly described. Ginseng has been labeled an “adaptogen” because it reputedly protects the body against stress and restores homeostasis. Because its pharmacologic actions are attributed to the ginsenosides, a group of compounds known as steroidal saponins, many commercially available ginseng preparations have been standardized to ginsenoside content.

The many heterogeneous and sometimes opposing effects of different ginsenosides give ginseng a broad but incompletely understood pharmacologic profile including general health, fatigue, immune function, cancer, cardiovascular disease, diabetes mellitus, cognitive function, viral infections, sexual function, and athletic performance. The underlying mechanism is similar to that classically described for steroid hormones. This herb decreases postprandial blood glucose in both healthy and type 2 diabetes patients, an effect that can create unintended hypoglycemia in patients who have fasted before surgery.

Ginseng can alter coagulation pathways. The antiplatelet activity of panaxynol, a constituent of ginseng, may be irreversible in humans. Ginseng extract and ginsenosides inhibit platelet aggregation in vitro and prolong thrombin time and activated partial thromboplastin time in in vivo animal models.

The clinical evidence implicating ginseng as a cause of bleeding is weak and based on only a few case reports. Although ginseng may inhibit the coagulation cascade, one case associated its use with a significant decrease in warfarin anticoagulation. Subsequently, a study in volunteers showed that American ginseng interfered with warfarin-induced anticoagulation, reducing its anticoagulant effect. When prescribing warfarin, clinicians should specifically ask about ginseng use. In another clinical trial, warfarin’s clearance was moderately increased with Asian ginseng. Because warfarin is often used after orthopedic or vascular procedures, this herbal drug interaction can affect perioperative management in many patients.

In rats, the elimination half-lives are different after an intravenous infusion of ginseng, with ginsenosides Re and Rg1 between 0.7 and 4 hours, and ginsenosides Rb1 and Rd between 19 and 22 hours. After oral administration of ginseng, ginsenoside Rb1 reached the maximum plasma concentration at approximately 4 hours with a prolonged half-life. These data suggest that ginseng should be discontinued at least 48 hours before surgery. Because platelet inhibition by ginseng may be irreversible, ginseng use should be stopped at least 2 weeks before surgery.

Green Tea

Tea from the Camellia sinensis is one of the most ancient and the second most widely consumed beverage in the world. Tea can be classified into different types, such as green, oolong, and black. Green tea, which is not fermented and is derived directly from drying and steaming fresh tea leaves, contains polyphenolic compounds. Catechins in green tea account for 16% to 30% of its dry weight. Epigallocatechin-3-gallate (EGCG), the most predominant catechin in green tea, is responsible for much of the biologic activity mediated by green tea.

In an early in vitro and in vivo study, both green tea and EGCG significantly prolonged mouse tail bleeding time in conscious mice. They inhibited adenosine diphosphate- and collagen-induced rat platelet aggregation in a dose-dependent manner. The antiplatelet activity can result from the inhibition of thromboxane A2 formation by preventing arachidonic acid liberation and thromboxane A2 synthase. Regarding a possible adverse effect of green tea on platelets, one case reported thrombotic thrombocytopenic purpura developed after a patient consumed a weight-loss product containing green tea. On the other hand, drinking green tea could antagonize the anticoagulant effects of warfarin because green tea contains vitamin K.

The half-life for EGCG in one study was between 1.9 and 4.6 hours and in another study was observed to be between 2.2 and 3.4 hours. Based on pharmacokinetic data and possible antiplatelet activity, green tea should be discontinued at least 7 days before surgery.

Kava

Kava is derived from the dried root of the pepper plant Piper methysticum . Kava has gained widespread popularity as an anxiolytic and sedative. The kavalactones appear to be the source of kava’s pharmacologic activity.

Because of its psychomotor effects, kava was one of the first herbal medications expected to interact with anesthetics. The kavalactones can have many effects such as: (1) dose-dependent effects on the central nervous system, including antiepileptic, neuroprotective, and local anesthetic properties; (2) act as a sedative-hypnotic by potentiating inhibitory neurotransmission of γ-aminobutyric acid (GABA); (3) increased barbiturate sleep time in laboratory animals, which might explain the mechanism of a coma attributed to an alprazolam-kava interaction ; (4) abuse potential, whether long-term use can result in addiction, tolerance, and acute withdrawal after abstinence is unknown; (5) increased γ-glutamyl transpeptidase levels with potential risk of hepatotoxicity ; and (6) produces “kava dermopathy,” characterized by reversible scaly cutaneous eruptions.

In an in vitro investigation, a kava compound (+)-kavain suppressed the aggregation of human platelets. Kava inhibits cyclooxygenase with the potential to decrease renal blood flow and to interfere with platelet aggregation. Consumption of kava has potential cardiovascular effects that could manifest in the perioperative period. Although kava has been banned in Europe since 2002, it is available in North America and many countries in the Pacific region. A concentration-based response relationship can occur with hepatotoxicity, even leading to numerous cases of liver transplantation.

Peak plasma levels occur 1.8 hours after an oral dose, and the elimination half-life of kavalactones is 9 hours. Unchanged kavalactones and their metabolites undergo renal and fecal elimination. Pharmacokinetic data and the possibility for enhancement of the sedative effects from anesthetics suggest that kava should be discontinued at least 24 hours before surgery. Earlier discontinuation probably should be considered when surgical procedures are expected to compromise hepatic function or blood flow.

Saw Palmetto

Saw palmetto, which is used by more than 2 million men in the United States to treat symptoms associated with benign prostatic hypertrophy, is of questionable efficacy for this purpose. The major constituents of saw palmetto are fatty acids and their glycerides (i.e., triacylglycerides and monoacylglycerides), carbohydrates, steroids, flavonoids, resin, pigment, tannin, and volatile oil. The pharmacologic activity of saw palmetto has not been attributed to a single compound.

Although the mechanism of action of saw palmetto is not known, multiple mechanisms have been proposed. Saw palmetto extract, like finasteride, inhibits 5α-reductase in vitro; however, results of in vivo studies have been inconsistent. Other proposed mechanisms are inhibition of estrogen and androgen receptors, binding of autonomic receptors, blocking of prolactin receptor signal transduction, interference with fibroblast proliferation, induction of apoptosis, inhibition of α ₁ -adrenergic receptors, and antiinflammatory effects.

In a patient undergoing craniotomy, saw palmetto was associated with excessive intraoperative bleeding that required termination of the procedure. Another case of hematuria and coagulopathy in a patient who used saw palmetto was reported. This complication was attributed to saw palmetto’s antiinflammatory effects, specifically the inhibition of cyclooxygenase and subsequent platelet dysfunction. Because there are no pharmacokinetic or clinical data for saw palmetto, specific recommendations for preoperative discontinuation cannot be made.

St. John ’ s wort

St. John’s wort is the common name for Hypericum perforatum, and has been used for mental health and depression conditions. A multicenter clinical trial concluded that St. John’s wort is not effective in the treatment of major depression. The compounds believed to be responsible for its pharmacologic activity are hypericin and hyperforin. Commercial preparations are often standardized to a fixed hypericin content of 0.3%.

St. John’s wort exerts its effects by inhibiting reuptake of serotonin, norepinephrine, and dopamine. Concomitant use of this herb with or without serotonin reuptake inhibitors can create a syndrome of central serotonin excess. Although early in vitro data implicated monoamine oxidase inhibition as a possible mechanism of action, a number of later investigations have demonstrated that monoamine oxidase inhibition is insignificant in vivo.

Use of St. John’s wort can significantly increase the metabolism of many concomitantly administered drugs, some of which are vital to the perioperative care of certain patients. There is induction of the cytochrome P450 3A4 isoform, and interactions with substrates of the 3A4 isoform, including indinavir sulfate, ethinylestradiol, and cyclosporine, have been documented. There are important clinical consequences of this metabolic effect, particularly in transplant patients. In two case reports of heart transplant patients, after taking St. John’s wort the patients’ plasma cyclosporine concentrations became subtherapeutic and acute transplant rejection resulted. After stopping St. John’s wort, plasma cyclosporine remained within the therapeutic range with no further episodes of rejection ( Fig. 33.1 ). In one series of 45 organ transplant patients, St. John’s wort was associated with an average 49% decrease in blood cyclosporine levels. Other P450 3A4 substrates commonly used in the perioperative period include alfentanil, midazolam, lidocaine, calcium channel blockers, and 5-hydroxytryptamine receptor antagonists. In addition, the cytochrome P450 2C9 isoform also may be induced, which results in decreased anticoagulant effect of warfarin, a substrate of the 2C9 isoform, in seven reported cases. Other 2C9 substrates include the nonsteroidal antiinflammatory drugs. Furthermore, the enzyme induction caused by St. John’s wort may be more pronounced when other enzyme inducers, which could include other herbal medications, are taken concomitantly. St. John’s wort also affects digoxin pharmacokinetics.

Cyclosporine concentrations in two patients (A and B) after heart transplantation. Treatment with St. John’s wort extract containing 900 μg of hypericin was associated with a drop in cyclosporine values below the therapeutic range and acute transplant rejection.

From Breidenbach T, Hoffmann MW, Becker T, et al. Drug interaction of St John’s wort with cyclosporine. Lancet . 2000;355:1912.

The single-dose and steady-state pharmacokinetics of hypericin, pseudohypericin, and hyperforin have been determined in humans. After oral administration, peak plasma levels of hypericin and hyperforin are achieved in 6.0 and 3.5 hours, respectively, and their median elimination half-lives are 43.1 and 9.0 hours, respectively. Long half-life and altered metabolism of many drugs make concomitant use of St. John’s wort a particular risk in the perioperative setting. Pharmacokinetic data suggest that this herbal medication should be discontinued at least 5 days before surgery. Discontinuation is especially important in patients awaiting organ transplantation or in those who might require oral anticoagulation postoperatively. Moreover, these patients should be advised to avoid taking St. John’s wort postoperatively.

Valerian

Valerian (Valeriana officinalis) is an herb that is native to temperate regions of the Americas, Europe, and Asia. It is used as a sedative, particularly in the treatment of insomnia, and virtually all herbal sleep aids contain valerian. Valerian contains many compounds acting synergistically, but the sesquiterpenes are the primary source of valerian’s pharmacologic effects. Commercially available preparations may be standardized to valerenic acid.

Valerian produces dose-dependent sedation and hypnosis. These effects are probably mediated through modulation of GABA neurotransmission and receptor function. Valerian increased barbiturate sleep time in experimental animals. In several randomized, placebo-controlled trials in humans, there was a mild subjective improvement in sleep with valerian, especially when used for 2 weeks or more. Objective tests have had less consistent results, with little or no improvement in sleep noted. In one patient, valerian withdrawal appeared to mimic an acute benzodiazepine withdrawal syndrome characterized by delirium, cardiac complications after surgery, and attenuation of the symptoms by administration of a benzodiazepine. Based on these findings, valerian should potentiate the sedative effects of anesthetics and adjuvants that act at the GABA receptor, such as midazolam.

The pharmacokinetics of valerian’s constituents have not been studied, although their effects may be short-lived. Abrupt discontinuation in patients who may be physically dependent on valerian risks benzodiazepine-like withdrawal. In these individuals, this herbal medication should be gradually decreased with close medical supervision over the course of several weeks before surgery. If such tapering is not feasible, physicians can advise patients to continue taking valerian until the day of surgery. Based on the mechanism of action and a reported case of efficacy, benzodiazepines can treat withdrawal symptoms should they develop in the postoperative period.

Other Herbal Medicines

In a survey conducted in 2007, the top 10 herbal medicines also included soy isoflavones, grape seed extract, and milk thistle. There are no reports of adverse effects or perioperative risks from these herbs.

Although boldo (Peumus boldus) , Danshen (Salvia miltiorrhiza) , Dong quai (Angelica sinensis) , and papaya (Carica papaya) are encountered less frequently, it may be prudent to discontinue their use 2 weeks before surgery because they have shown antiplatelet aggregation activity and herb-drug interactions.

Common Dietary Supplements

Herbal medicines fall into the broader category of dietary supplements that also includes vitamins, minerals, amino acids, enzymes, animal extracts, prebiotics, and probiotics. Data on the safety of these agents in the perioperative period are scant. High-dose vitamin use, particularly of the fat-soluble vitamins (i.e., A, D, E, and K), can be associated with acute and chronic toxicity. Drug interactions for coenzyme Q ₁₀ , glucosamine, chondroitin, sulphate, and fish oil have been sufficiently documented to merit inclusion in this chapter. Prebiotics and probiotics have become increasingly popular in research, in the context of the rapidly evolving field of gut microbiome, adding to the current knowledge of perioperative medicine.

Glucosamine and Chondroitin Sulfate

Glucosamine and chondroitin sulfate are widely used for joint disorders by many patients undergoing orthopedic procedures. Although their mode of action may be complex, glucosamine and chondroitin sulfate have been widely accepted as supplements in the management of osteoarthritis (OA) because they are the essential components of proteoglycan in normal cartilage. When a large-scale trial evaluated glucosamine and chondroitin sulfate alone or in combination, pain was not reduced in a group of patients with OA of the knee. Exploratory analyses suggested that the two in combination might be effective in a subgroup of patients with moderate-to-severe knee pain.

Long-term clinical data regarding the safety of glucosamine and chondroitin sulfate alone or in combination are limited. Use of chondroitin sulfate alone is well tolerated and without significant adverse drug interaction. One concern regarding the use of glucosamine is its potential to cause or worsen diabetes in animal models ; this effect is supported by clinical studies. In a report from the FDA MedWatch database, there were 20 cases of complications involving glucosamine or glucosamine-chondroitin sulfate use with warfarin. Coagulation was altered as manifested by increased INR or increased bleeding or bruising.

When glucosamine is taken orally, 90% is absorbed. Because of extensive first-pass metabolism, only 25% bioavailability is achieved by oral administration compared with bioactivity of 96% with intravenous administration. Peak plasma levels occurred 4 hours after an oral dose and declined to baseline after about 48 hours. Chondroitin sulfate was absorbed slowly after oral ingestion with a plasma peak at 8.7 hours and decline to baseline at about 24 hours. Considering the reported interaction between glucosamine-chondroitin and warfarin, these supplements should be discontinued 2 weeks before surgery, especially if warfarin will be given during the perioperative period.

Fish Oil

Intake of fish oil supplements containing omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) reduces the incidence of many chronic diseases that involve inflammatory processes, including cardiovascular diseases, inflammatory bowel disease, cancer, rheumatoid arthritis, and neurodegenerative illnesses. However, omega-3 fatty acid did not reduce the rate of death in patients with cardiovascular risk in one study. A metaanalysis of efficacy also concluded that omega-3 polyunsaturated fatty acid supplementation does not decrease the risk of all-cause mortality, cardiac death, sudden death, myocardial infarction, or stroke based on relative and absolute measures of association. This article included many studies of patients with complex risk factors.

Omega-3 fatty acids, however, can inhibit platelet aggregation and increase bleeding risk by the following studies: (1) In vitro experiments have demonstrated an antiplatelet aggregate effect, and inhibition correlated with platelet cyclic adenosine monophosphate levels. (2) In vivo studies have showed decreased platelet aggregation but do not influence bleeding time. (3) The inhibition of platelet aggregation was gender specific in a clinical study.

Although evidence for significant bleeding concerns is not found in clinical trials, several case reports have illustrated a possible interaction between warfarin and omega-3 fatty acids. Extremely elevated INR associated with warfarin in combination with omega-3 fatty acids was found in two cases. These reports suggest that fish oil be discontinued 2 weeks before surgery, especially for patients taking large doses.

Prebiotics and Probiotics

A prebiotic is a nondigestible food ingredient that beneficially affects the host by selectively stimulating the growth and activity of one or a limited number of bacteria in the colon that has the potential to improve host health. A probiotic is a live microbial feed supplement that beneficially affects the host by improving its intestinal microbial balance. Both prebiotics and probiotics can perturbate the gut microbiota, a consortium of diverse microorganisms residing in the gastrointestinal tract, with significant influence in energy metabolism, immune system development, neurologic function, and behaviors. Research on gut microbiota has made significant progress in recent years owing to the technological advancement of next-generation DNA sequencing and high-throughput data processing.

Targeting gut microbiota using fecal transplantation or fecal capsules to treat recurrent Clostrisium difficile infection is under intense investigation, with a few trials indicating promising results. However, a recent trial comparing oral probiotics with oral antibiotics for elective colorectal surgery showed that conventional oral antibiotics preparation in addition to mechanical bowel preparation is better than oral probiotics with mechanical bowel preparation. Studies have implicated gut microbiota in visceral hypersensitivity (irritable bowel syndrome), inflammatory pain, and more recently, neuropathic pain. Moreover, gut microbiota have been shown to modulate the central nervous system function, including anxiety/depression and cognition. Despite the rapidly evolving field of gut microbiome, data on perioperative use of prebiotics and probiotics are scarce. Future research is warranted to investigate potential roles of prebiotics and probiotics in the perioperative setting, particularly in volatile anesthetics sensitivity, postoperative pain control, and postoperative cognitive dysfunction.

Mechanism and General Practice

Although acupuncture can reduce preoperative anxiolysis, intraoperative anesthetic requirements, and postoperative ileus, and can support cardiovascular function, it has been most widely studied to control postoperative pain and to prevent or treat nausea and vomiting.

Acupuncture has been used in China for more than 3000 years, and in the 1970s, it gained international attention as a treatment for a variety of diseases. In 1974, Dr. Bonica became the first pain physician invited by the Chinese government as a member of an American medical delegation to assess the utility of acupuncture in surgical procedures. He witnessed more than 28 surgeries personally and spoke with a large number of surgeons as well as anesthesia providers. In the report subsequently published in JAMA, he pointed out, “it (acupuncture) may prove extremely useful in relieving postoperative pain thus obviating the depressant effects of narcotics usually employed for this purpose.” Traditional Chinese medicine (TCM) is the basis for acupuncture practice. According to TCM, the human body operates on 12 bilaterally distributed channels (6 yin channels and 6 yang channels) in conjunction with two midline channels in the ventral and dorsal aspects of the body, respectively. Acupuncture is the stimulation of anatomic locations on the skin by a variety of techniques that can be classified as invasive (e.g., needles, injections) or noninvasive (e.g., transcutaneous electrical stimulation, pressure, laser). Needles inserted into the skin can be stimulated by manual manipulation, moxibustion (i.e., burning a substance to produce heat), pressure, laser, and electricity. A scientific basis may exist for acupuncture. Acupuncture stimulates high-threshold, small-diameter nerves that activate the spinal cord, brainstem (i.e., periaqueductal gray area), and hypothalamic (i.e., arcuate) neurons, which trigger endogenous opioid mechanisms. The effect of acupuncture analgesia can be reversed by administration of naloxone. Other mechanisms such as modulation of immune function, inhibition of the inflammatory response, regulation of neuropeptide gene expression, and alteration in hormonal levels have been proposed. The development of neuroimaging tools, such as positron emission tomography and functional magnetic resonance imaging (fMRI), make noninvasive studies of acupuncture’s effects on human brain activity possible. Studies using positron emission tomography have demonstrated that the thalamic asymmetry present in patients suffering from chronic pain was reduced after acupuncture treatment. Other studies using fMRI have pointed to relationships between particular acupoints and activation of the visual cortex. Using a noninvasive imaging technique called Bi-Digital O-Ring Test, researchers found that each meridian is connected to a representative area in the cerebral cortex, suggesting that the meridian system defined in the theories of Chinese medicine may overlap with distinct supraspinal regions. Electroacupuncture, particularly at low frequency, is associated with widespread fMRI signal increases in the anterior insula area, limb, and paralimbic structures. These humoral and neuronal changes induced by acupuncture form the basis for its clinical use.

According to the Centers for Disease Control and Prevention, more than 50 million procedures are performed each year in the United States, including more than 1 million hip and knee replacements. Most surgical procedures are associated with postoperative pain, for which opioids are the mainstay of treatment. However, opioid usage is associated with a high incidence of side effects including respiratory depression, reduced gastrointestinal motility, sedation, and itching. Chronic exposure to high-dose opioids can also induce opioid tolerance and dependence. It is therefore highly desirable to develop alternative therapies that provide adequate postoperative pain relief with minimal side effects. In this context, acupuncture for acute postoperative pain control has gained significant interest, including its use for oral-maxillofacial and neck surgeries, sternotomy/thoracotomy, abdominal/pelvic surgeries, and orthopedic and spine surgeries. Studies have shown that acupuncture can lead to improved pain scores or reduced opioid requirements postoperatively. Lao and associates carried out a randomized, double-blinded, and placebo-controlled trial on postoperative dental pain ( N = 39). The acupuncture group received acupuncture for about 20 minutes with intermittent manual manipulation to trigger “De Qi” sensation—a sensation of numbness, distension, or electrical tingling at the needling site. The control group underwent placebo acupuncture treatment at the identical acupuncture points to the acupuncture group but without needle insertion into the skin. Mean pain-free postoperative time was significantly longer in the acupuncture group (172.9 minutes) than in the placebo group (93.8 minutes). Pain medication requirements were significantly less in the acupuncture group than in the control group. Of note, this study also ruled out psychological variables as confounders for their observed benefits of acupuncture.

It is important to note that many of the studies on clinical applications of acupuncture have insufficient sample size, high dropout rates, inadequate follow-up, and poorly defined illnesses, enrollment criteria, and outcome measures. Additionally, many of the clinical trials are single center studies, which could potentially demonstrate larger treatment effects than multicenter studies.

Side effects of acupuncture treatments include bruising or bleeding at the needle insertion site, transient vasovagal response, infection, dermatitis, and retained needle fragments. The occurrence of adverse events during acupuncture treatment is considered extremely low. In a survey that included 34,407 acupuncture treatments, there were no reported events of serious side effects and only 43 cases of significant mild side effects were noted, such as nausea, fainting, and bruising. Recently, the safety of acupuncture was confirmed in a cohort of cancer patients with thrombocytopenia.

Acupuncture for Postoperative Nausea and Vomiting

One of the most promising indications for acupuncture is to prevent postoperative nausea and vomiting (PONV). PONV results in patient dissatisfaction, delayed discharge, unanticipated hospital admission, and the use of resources. Drugs have been the mainstay of management, however these have limited effectiveness, are associated with adverse effects, and can be costly. Acupuncture prevents PONV compared with sham acupuncture or no treatment. In two early controlled trials, acupuncture prevented PONV in the pediatric population ; however, one literature review of 10 research studies examining the use of acupressure and acupuncture in adults concluded that it is not effective in preventing and managing PONV. Other clinical studies have found that acupuncture prevents PONV and results in a greater degree of adult patient satisfaction. For many of the trials in both adults and children, the PONV acupuncture point was P6 or PC6 (i.e., Nei guan or Pericardium 6). The P6 acupuncture point is located between the palmaris longus and flexor carpi radialis muscle tendons, 4 cm proximal to the distal wrist crease and 1 cm below the skin ( Fig. 33.2 ). Intraoperative stimulation of the P6 acupuncture point reduced the incidence of PONV, and its efficacy was similar to that of antiemetic drugs. Stimulation of the acupuncture point should be initiated before induction of anesthesia. Postoperative stimulation may be just as or more effective. In children, stimulation immediately before emergence and in the recovery room has been effective. A recent metaanalysis for pediatric tonsillectomy indicated that acupuncture at the P6 acupuncture point is effective in preventing PONV. Some anesthesiologists anecdotally report tapping a small needle cap or other piece of smooth plastic over the P6 point as an effective means of acupressure stimulation.

The P6 acupuncture point is located between the palmaris longus and flexor carpi radialis muscle tendons, 4 cm proximal to the distal wrist crease and 1 cm below the skin.

Studies often differ in acupuncture method: duration and timing of stimulation, unilateral versus bilateral stimulation, and type of stimulation (i.e., needles with or without additional stimulation, acupressure, transcutaneous electrical stimulation, cutaneous laser stimulation, injection of a 50% dextrose solution, or capsicum plaster). Data to compare the effectiveness, safety, and costs of different methods of stimulation are inadequate.

Deep Breathing

Deep breathing exercises are performed as part of a relaxation technique. With this method, a subject consciously slows breathing and focuses on taking deep breaths. Deep breathing can help reduce abdominal and surgical pain.

Studies of postoperative pain relief with breath control were reported in the 1970s. Since then, many studies have reported its efficacy against postoperative pain in adult patients ; prevented postoperative pulmonary complications ; and decreased pain in pediatric patients.

Fast or forced deep breathing can also increase postoperative pain. Thus, those who assist patients in postoperative pain management should encourage deep breathing exercises that are performed slowly, smoothly, and gently. Slow, deep breathing relaxation exercises have been used successfully as an adjunct to opioids for postoperative pain management in patients who had coronary bypass surgery ; however, after abdominal surgery, deep breathing was ineffective for pain reduction in older patients because pulmonary complications developed postoperatively. Most patients who receive deep breathing education think it is useful, and the exercise was effective in increasing their feelings of rapport with staff and intention to follow their doctor’s directives. Results from a recent trial demonstrated that slow, deep breathing had analgesic effects with increased vagal cardiac activity. Slow, deep breathing relaxation can also decrease the sensation of postoperative nausea.