Acupuncture-Point

Downloaded by Chulalongkorn Univ from www.liebertpub.com at 08/24/18. For personal use only. THE JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE Volume 12, Number 5, 2006, pp. 489–495 © Mary Ann Liebert, Inc. EDUCATION, INITIATIVES, AND INFORMATION RESOURCES Cochrane Systematic Reviews Examine P6 Acupuncture-Point Stimulation for Nausea and Vomiting JEANETTE EZZO, M.P.H., Ph.D.,1 KONRAD STREITBERGER, M.D.,2 and ANTONIUS SCHNEIDER, M.D.3 ABSTRACT Background: In 1998, the National Institutes of Health Consensus Statement on Acupuncture concluded that promising results have emerged showing the efficacy of acupuncture in adult postoperative and chemotherapy induced nausea and vomiting. The acupuncture point, P6 had been the point used in most of the trials. Objectives: To summarize Cochrane systematic reviews assessing P6 stimulation for nausea and vomiting. Results: Reviews were found on postoperative sickness, chemotherapy-induced nausea and vomiting, and pregnancy-related nausea and vomiting. Results for postoperative nausea and vomiting show the most consis- tent results with 26 trials and more than 3000 patients showing the superiority of real P6 stimulation over sham for both adults and children and for both nausea and vomiting. Pooled data of trials including different antiemet- ics showed that P6 stimulation seems to be superior to antiemetic medication for nausea and equivalent for vomiting. P6 stimulation was similarly effective across the different methods of stimulation, both invasive or noninvasive. Results for chemotherapy-induced nausea and vomiting showed 11 trials and over 1200 patients. Electroacupuncture, but not manual acupuncture, was beneficial for first-day vomiting. Acupressure was ef- fective for first-day nausea but not vomiting. Wristwatch-like electrical devices were not effective for any out- come. Results for pregnancy-related nausea and vomiting comprised six trials and approximately 1150 patients. Results were mixed with some trials showing positive and other trials equivocal results with no favor to a cer- tain kind of method. Conclusions: P6 stimulation may be beneficial for various conditions involving nausea and vomiting. The added value to modern antiemetics remains unclear. In patients on chemotherapy, future research should focus on patients for whom the problems are refractory. The next steps in research should include investigating whether acupuncture points added to P6 or individualizing treatment based on a Traditional Chinese Medicine diagno- sis increases treatment effectiveness. It would also be worthwhile to identify predictors of response across the different conditions so that the individual patients can optimize acupuncture point therapy. 1JPS Enterprises, Baltimore, MD. 2Department of Anaesthesiology, University of Heidelberg, Heidelberg, Germany. 3Department of General Practice and Health Services Research, University of Heidelberg, Germany. The Cochrane Complementary Medicine (CM) Field is the central group within the Cochrane Collaboration that facilitates the con- duct of Cochrane CM reviews. The CM Field represents an international commitment by researchers, clinicians, consumers, and CM practitioners from nearly every continent to define the evidence base of CM. It is headquartered at the Complementary Medicine Pro- gram University of Maryland School of Medicine, 2200 Kernan Drive, Kernan Hospital Mansion, Baltimore, MD 21207-6697 USA. For more information contact Eric Manheimer at [email protected]. The CM Field website is www.compmed. umm.edu/Cochrane/index.html 489

490 EZZO ET AL. Downloaded by Chulalongkorn Univ from www.liebertpub.com at 08/24/18. For personal use only. INTRODUCTION device that provides noninvasive electrostimulation. Pres- sure can be applied either by pressing on the point with the There is perhaps no acupuncture point that has been as fingers or by wearing a SeaBand™ (Sea-Band Ltd., Leices- extensively studied as P6, the antinausea point. To study tershire, England), an elastic wristband with an embedded P6, researchers have given cyclophosphamide to ferrets1; stud to provide acupressure). healthy human volunteers have been optokinetically stimu- lated to the point of motion sickness2; and more than 6000 PONV patients have participated in randomized trials (Table 1). While PONV is not life-threatening, patients often report The interest in P6 began in 1986 when Dundee, an anes- more discomfort with nausea and vomiting than with post- thesiologist, first reported in the British Medical Journal that operative pain. The incidence of PONV ranges from 30% he had successfully used P6 to prevent postoperative nau- to 79%.10 The most effective antiemetics appear to be sero- sea and vomiting (PONV).3 During a previous visit in China tonin antagonists and dexamethasone, alone or in combina- in 1983, Dundee had been impressed by the use of acu- tion. In addition to these drugs, recommendations for pressure to prevent morning sickness, and he became fasci- prophylaxis of PONV also include nonpharmocologic tech- nated by the idea of using P6-acupuncture for prevention of niques, such as acupuncture, acupressure, and transcuta- PONV. neous nerve stimulation.11 Dundee’s initial publication spawned a decade of ran- The Cochrane review of postoperative nausea and vom- domized trials on P6 culminating in a systematic review of iting contains 26 trials, involving, collectively, more than 33 trials with 27 favoring P6.4 Influenced by this review, 3300 patients6 (Table 1). Compared to sham procedures, the National Institutes of Health (NIH) Consensus Confer- P6 acupuncture-point stimulation was more effective in ence on Acupuncture concluded that “promising results have preventing nausea (relative risk [RR] 0.72; 95% confi- emerged showing the efficacy of acupuncture in adult post- dence interval [CI] 0.59–0.89) and vomiting (RR 0.71; operative and chemotherapy induced nausea and vomiting”.5 95% CI 0.56–0.91). The effect was similar between chil- For no other condition had acupuncture accrued such a large dren and adults. Nine trials compared P6 to various amount of positive data. antiemetics. The pooled results showed that P6 was supe- rior to medication in preventing nausea and equivalent in At the time of the NIH conference, however, the newest preventing vomiting (Table 1). However, these results antiemetics, 5-HT3 antagonists such as granisetron and on- should be interpreted with caution because a variety of dansetron, were just beginning to be used widely. The ad- antiemetics were pooled including a trial of metoclo- vent of these drugs has raised questions about the relative pramide, which is not currently recognized as effective for contribution of P6. PONV prophylaxis. Thus the relative benefit of P6 com- pared to antiemetics remains unclear. There are Cochrane reviews on P6 for PONV,6 One of the most notable findings was that P6 stimulation chemotherapy-induced nausea and vomiting (CNV),7 and was similarly effective across methods of stimulation pregnancy-related nausea and vomiting (PRNV).8 whether they were invasive (acupuncture) or noninvasive (acupressure or wristwatch-like electrical stimulation). This Pericardium 6 (P6) is helpful information to patients because the postoperative patients can use the most convenient, self-administered P6 is located on the anterior surface of the wrist between modality such as acupressure bands rather than relying on the tendons of the flexor carpi radialis and the palmaris acupuncturists. longus, next to the median nerve. P6 is usually measured as three finger breadths of the patient from his or her flexor CNV crease. For an average adult, this is 3–5 cm proximal to the flexor crease. While other acupuncture points also have The American Society of Clinical Oncology (ASCO) rec- antiemetic effects, none have been studied to the same ex- ommends 5-HT3 receptor antagonists plus corticosteroids tent as P6. A summary of the other points and the mecha- prior to giving patients highly emetogenic chemotherapy. nism of action of P6 have been discussed elsewhere.9 Chemotherapy-induced nausea and vomiting is classified as either acute (within 24 hours postchemotherapy) or delayed Stimulation (greater than 24 hours but less than 7 days postchemother- apy). While these newer medications have greatly reduced P6 can be stimulated by various methods. The most well- chemotherapy-induced sickness, many patients on chemo- known technique is manual stimulation by insertion and therpay still experience acute and/or delayed nausea and manual rotation of a very fine needle (manual acupuncture). An electrical current can be passed through the inserted nee- dle (electroacupuncture). Electrical stimulation can also be applied via electrodes on the skin surface or by a Relief- Band,™ (Woodside Biomedical, Inc., Abbott Park, IL, and Maven Laboratories, Citrus Heights, CA) a wristwatch-like

Downloaded by Chulalongkorn Univ from www.liebertpub.com at 08/24/18. For personal use only. TABLE 1. RESULTS OF COCHRANE P6 REVIEWS: EFFECT SIZES AND PLAIN LANGUAGE SUMMARIES Cochrane Nausea Vomiting Plain language summary reviewa Postoperative Compared to sham Compared to sham This review found evidence to support the use of P6 acupoint stimulation in RR 0.72; 95% CI 0.59– RR 0.71; 95% CI 0.56– preventing postoperative nausea and vomiting (PONV) with minimal NV6 0.89; p ϭ 0.002* side-effects. 0.91; p ϭ 0.007* 26 trials Compared to medication Postoperative nausea and vomiting (PONV) are two of the most common 3347 patients RR, 0.70; 95% CI, 0.50– Compared to medication complications after surgery and anaesthesia. Drug therapy is only partially 0.98; p ϭ not provided* RR, 0.92; 95% CI, 0.65– effective in preventing PONV and may cause adverse effects. Alternative Chemotherapy- methods, such as stimulating an acupuncture point on the wrist (P6 acupoint induced NV7 Acute nausea 1.29; p ϭ not provided stimulation), have been studied in many trials. The use of P6 acupoint 11 trials stimulation can reduce the risk of nausea and vomiting after surgery, with 1230 patients Manual acupuncture: Acute vomiting minimal side-effects. Compared with antiemetic prophylaxis, P6 acupoint SMD 0.02; 95% CI stimulation seems to reduce the risk of nausea but not vomiting. 0.42–0.46, p ϭ 0.9 Manual acupuncture RR 0.54; 95% CI, 0.17–1.71, Electroacupuncture is effective for first day vomiting after chemotherapy, Electroacupuncture: p ϭ 0.3 but trials considering modern antivomiting drugs are needed. No trials Electroacupuncture: This review looked at whether stimulating acupuncture points could reduce Acupressure: RR 0.76; 95% CI 0.60– nausea and vomiting caused by chemotherapy. Acupuncture points can be SMD 0.19; 95% CI, Ϫ0.38– 0.97; p ϭ 0.02* stimulated by acupuncture applied with electricity (electroacupuncture), 0.01; p ϭ 0.03* acupuncture without electricity (manual acupuncture), acupressure Acupressure: (pressing on the points usually with fingertips), or electricial stimulation Noninvasive ES: RR 0.83; 95% CI 0.60–1.16; on the skin surface such as wristwatch-like devices. Electroacupuncture SMD Ϫ0.07; 95% CI,Ϫ0.23– p ϭ 0.3 reduced first-day vomiting, but manual acupuncture did not. Acupressure 0.10; p ϭ 0.4 reduced first-day nausea, but was not effective on later days. Acupressure Noninvasive ES: showed no benefit for vomiting. Electrical stimulation on the skin showed Delayed nausea RR 0.90; 95% CI, 0.67–1.19; no benefit. All trials also gave antivomiting drugs, but the drugs used in the Manual acupuncture: p ϭ 0.4 electroacupuncture trials were not the most modern drugs, so it is not known No trials if electroacupumcture adds anything to modern drugs. Trials of Delayed vomiting electroacupuncture with modern drugs are needed. Electroacupuncture: Manual acupuncture: No trials No trials (continued ) Acupressure: Electroacupuncture: SMD Ϫ0.05; 95% CI, Ϫ0.22– No trials 0.13; p ϭ 0.6 Acupressure: Noninvasive ES: WMD Ϫ0.07 95% CI, Ϫ0.25– SMD 0.03; 95% CI, 0.14– 0.11; p ϭ 0.4 0.19, p ϭ 0.7 Noninvasive ES: WMD 0.06; 95% CI, Ϫ0.11– 0.22, p ϭ 0.5

Downloaded by Chulalongkorn Univ from www.liebertpub.com at 08/24/18. For personal use only. TABLE 1. RESULTS OF COCHRANE P6 REVIEWS: EFFECT SIZES AND PLAIN LANGUAGE SUMMARIES (CONTINUED) Cochrane Nausea Vomiting Plain language summary reviewa Pregnancy- Prevention of morning Vomiting score Drugs do help sickness in early pregnancy, but acupressure and ginger induced NV8 sickness may work with no side-effects Compared to sham: Compared to sham: 6 trials OR 0.35; 95% CI, 0.12– WMD, Ϫ0.31; 95% CI, Ϫ0.76– Many women have sickness and vomiting in early pregnancy. Women with 1148 patients 1.06; p ϭ 0.6 0.14; p ϭ 0.2 persistent vomiting may need to be given extra fluids. Many drugs have been tried. Antihistamines work well but are likely to make women feel Compared to no treatment: Compared to no treatment: sleepy. One widely used pill (Debendox/Bendectin) using an antihistamine OR 0.25; 95% CI, 0.14– WMD, Ϫ0.30; 95% CI, Ϫ0.79– combined with vitamin B6 was withdrawn after its use was linked to limb 0.43; p ϭ 0.00001* 0.19; p ϭ 0.2 defects in babies; but this was not confirmed by later research. Vitamin B6 (pyridoxine) on its own may work but the evidence is not very strong. Acupressure (sea bands) could help, so may ginger, and more research is now being done. aSuperscript numbers represent text references. *Significant finding at the p Ͻ 0.05 level. NV, nausea and vomiting; RR, relative risk; CI, confidence interval; SMD, standardized mean difference; ES, electrostimulation; WMD, weighted mean difference; OR, odds ratio.

P6 ACUPOINT STIMULATION FOR NAUSEA AND VOMITING 493 Downloaded by Chulalongkorn Univ from www.liebertpub.com at 08/24/18. For personal use only. vomiting.12 The need for additional relief has led to renewed and vomiting have produced the same outcomes.13,14 It may interest in P6. be that, to influence vomiting, stronger forms of P6 stimu- lation, such as electroacupuncture, rather than weaker forms, The Cochrane review of chemotherapy-induced nausea such as acupressure, are needed. and vomiting contains 11 trials, involving, collectively, more than 1200 patients.7 One of the most notable findings Delayed nausea remains a problem even with the use of was that the method of P6 stimulation appears to produce current antiemetics, and many patients report that their worst different results. day of sickness is 2 or 3 days after chemotherapy. It is not known why delayed symptoms are so difficult to treat even Acupuncture with conventional medicines but it is apparent that acupres- sure offers little for delayed nausea. Manual and electroacupuncture trials combined reduced the proportion of patients experiencing acute vomiting Noninvasive electrostimulation (RR ϭ 0.74; 95% CI 0.58–0.94; p ϭ 0.01). When analyzed separately, electroacupuncture showed a benefit for ad- The most surprising results came from the trials using non- dressing acute vomiting but manual acupuncture did not invasive electrostimulation, primarily using wristwatch-like (Table 1). However, the manual acupuncture trial used mod- devices, which administered ongoing stimulation to P6. The ern antiemetics with acupuncture while the electroacupunc- pooled results showed no benefit over placebo for any nausea ture trials had used older antiemetic medications. The doses or vomiting score. Because all these trials gave concomitant of acupuncture were also very different in the two trials, modern antiemetics to both groups, the conclusions were that making it impossible to know how much of the difference these devices appear to add nothing to modern antiemetics. resulted from the medication differences and how much re- sulted from the acupuncture doses. In the manual acupunc- PRNV ture trial, one point was stimulated until de qi was elicited, and then needles were left in place for 20 minutes with no Approximately half of pregnant women will experience further stimulation. By contrast, the electroacupuncture trial nausea and vomiting in early pregnancy. While drugs are stimulated two points (P6 and ST36) by passing an electri- available, some pregnant women wish to avoid or minimize cal current through the needles continuously for 20 minutes. the use of drugs and, hence, turn to P6. These differences have raised important acupuncture dos- The Cochrane review of PRNV contains six trials, in- ing questions: Is longer stimulation better than shorter du- volving, collectively, approximately 1200 patients8 (Table ration of stimulation when trying to counteract highly eme- 1). Of the six trials, four presented data that could not be togenic agents such as chemotherapy? Is stimulation of P6 pooled. For dichotomous data assessing the presence or ab- and an additional point more effective than P6 alone? Is elec- sence of morning sickness, P6 was significantly more ef- troacupuncture preferred over manual acupuncture because fective than no treatment (odds ratio [OR] ϭ 0.25, 95% CI of electroacupuncture’s ability to stimulate more than one 0.14–0.43; p Ͻ 0.00001) or sham treatment (OR ϭ 0.35; point continuously? 95% CI 0.12–1.06; p ϭ 0.06). The authors stated: “These effects are comparable to those obtained with drugs.” How- There were no electroacupuncture data for delayed vom- ever, for continuous data (severity of nausea, frequency of iting or any nausea outcomes. There were also no elec- vomiting), there was no benefit observed. The authors, there- troacupuncture trials that used concurrent modern antiemet- fore, cited the evidence as “mixed.” ics. Therefore, while the effectiveness of electroacupuncture shows a proof of principle for preventing acute vomiting, One possible reason for the discrepancy of the findings studies that combine electroacupuncture with modern may lie in the timing of the outcomes. Dundee had observed antiemetics are needed to determine if electroacupuncture that the effects of P6 stimulation attenuate over a few hours. can confer additional benefit to modern antiemetics and to The trials with positive results appear to have taken the at- patients with refractory problems. tenuation into consideration. One trial used a continuous method of P6 stimulation through wristbands15 and the other Acupressure trial used intermittent stimulation every 4 hours each morn- ing of the study.16 These methods may be superior to stim- Acupressure showed benefit for acute nausea but not for ulating P6 once every 2 or 3 days as was done in some of vomiting or for delayed nausea (Table 1). This benefit was the equivocal trials. Given the attenuation effect, the timing noted in trials that also used concurrent modern antiemetics. of the outcome assessment is important. Some of the equiv- Acupressure, therefore, may offer an inexpensive, convenient, ocal studies17,18 appear to have measured the outcome 2 to self-administered intervention for patients on chemotherapy to 3 days after P6 stimulation, a time that may well have been reduce nausea on the first day of chemotherapy. beyond the therapeutic window. It is not clear why acupressure was effective for nausea and not vomiting but some trials for other kinds of nausea

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