Acupressure for Chemotherapy-Induced Nausea and Vomiting: A Randomized Clinical Trial

Transcription

1 This material is protected by U.S. copyright law. Uauthorized reproductio is prohibited. To purchase quatity reprits, please or to request permissio to reproduce multiple copies, please Acupressure for Chemotherapy-Iduced Nausea ad Vomitig: A Radomized Cliical Trial Suzae L. Dibble, DNSc, RN, Judy Luce, MD, Bruce A. Cooper, PhD, Jill Israel, RN, Misha Cohe, LAc, OMD, Breda Nussey, BA, ad Hope Rugo, MD Purpose/Objectives: To compare differeces i chemotherapyiduced ausea ad vomitig (CINV) amog three groups of wome (acupressure, placebo acupressure, ad usual care) udergoig chemotherapy for breast cacer. Desig: A multiceter, logitudial, radomized cliical trial throughout oe cycle of chemotherapy. Settig: Te commuity cliical ocology programs associated with the Uiversity of Texas M.D. Aderso Cacer Ceter ad ie idepedet sites located throughout the Uited States. Sample: 160 wome who were begiig their secod or third cycle of chemotherapy for breast cacer treatmet ad had moderate ausea itesity scores with their previous cycles. Methods: Subjects were radomized to oe of three groups: acupressure to P6 poit (active), acupressure to SI3 poit (placebo), or usual care oly. Subjects i the acupressure group were taught to apply a acupressure wrist device by research assistats who were uaware of the active acupressure poit. All subjects completed a daily log for 21 days cotaiig measures of ausea ad vomitig ad recordig methods (icludig atiemetics ad acupressure) used to cotrol these symptoms. Mai Research Variables: Acute ad delayed ausea ad vomitig. Results: No sigifi cat differeces existed i the demographic, disease, or treatmet variables amog the treatmet groups. No sigificat differeces were foud i acute ausea or emesis by treatmet group. With delayed ausea ad vomitig, the acupressure group had a statistically sigifi cat reductio i the amout of vomitig ad the itesity of ausea over time whe compared with the placebo ad usual-care groups. No sigifi cat differeces were foud betwee the placebo ad usual-care groups i delayed ausea or vomitig. Coclusios: Acupressure at the P6 poit is a value-added techique i additio to pharmaceutical maagemet for wome udergoig treatmet for breast cacer to reduce the amout ad itesity of delayed CINV. Implicatios for Nursig: Acupressure is a safe ad effective tool for maagig delayed CINV ad should be offered to wome udergoig chemotherapy for breast cacer. Key Poits... Nausea, especially delayed ausea, cotiues to be a problem for may wome udergoig chemotherapy for breast cacer. The amout ad itesity of ausea are greater amog youger wome. A umeric ratig scale is a appropriate daily measure of delayed ausea. I 2007, a estimated 8,480 wome i the Uited States are expected to be diagosed with breast cacer (America Cacer Society, 2007). May wome are treated with moderate to highly emetogeic chemotherapy, icludig doxorubici ad cyclophosphamide with or without 5-fluorouracil. Despite recet pharmaceutical advaces i the prevetio ad treatmet of chemotherapy-iduced ausea ad vomitig (CINV), may patiets cotiue to experiece sigificat delayed ausea ad some vomitig. Nausea ad vomitig have bee idetified as cotributig to patiets reluctace to begi chemotherapy ad may result i the discotiuatio of potetially effective treatmet strategies (Carr et al., 85; Dibble, Casey, Nussey, Israel, & Luce, 2004; Dibble, Israel, Nussey, Casey, & Luce, 2003; Rhodes & McDaiel, 97). Small studies of acupressure (Dibble, Chapma, Mack, & Shih, 2000; Dudee & Yag, 90; Staard, 89) have suggested that pressure o the ei gua (P6) poits may be a effective method to reduce CINV i wome udergoig chemotherapy. Some of the studies were cited i a recet Cochrae review (Ezzo et al., 2006) that supported the use of acupressure at P6 for ausea cotrol. Suzae L. Dibble, DNSc, RN, is professor emerita at the Istitute for Health ad Agig i the School of Nursig at the Uiversity of Califoria, Sa Fracisco (UCSF), ad presidet of Dibble Cosultig Corporatio i Sa Mateo, CA; Judy Luce, MD, is a professor i the Divisio of Hematology/Ocology i the School of Medicie at Sa Fracisco Geeral Hospital Medical Ceter; Bruce A. Cooper, PhD, is a seior statisticia i the Office of Research ad a associate adjuct professor i Commuity Health Systems at UCSF; Jill Israel, RN, is a research urse i the Departmet of Pulmoary ad Critical Care at Sa Fracisco Geeral Hospital Medical Ceter; Misha Cohe, LAc, OMD, is a assistat researcher i Itegrative Medicie at the Istitute for Health ad Agig i the School of Nursig at UCSF, the research/educatio chair at the Qua Yi Healig Arts Ceter i Sa Fracisco, ad the cliic director of Chicke Soup Chiese Medicie i Sa Fracisco; Breda Nussey, BA, is a programmer/aalyst at the Istitute for Health ad Agig i the School of Nursig at UCSF; ad Hope Rugo, MD, is a professor i the Divisio of Hematology ad Ocology i the Departmet of Medicie at UCSF. This study was fuded by the Natioal Cacer Istitute (RO1-840) ad the Commuity Cliical Ocology Program (U CA ). (Submitted July Accepted for publicatio March 4, 2007.) Digital Object Idetifier:.18/07.ONF

2 Acupressure is oivasive pressure applied by the thumbs, figers, ad hads o the surface of the ski at key poits (active acupressure). The mechaism of acupressure is based o a theory that is very differet from Wester medicie (Craze & Fou, 98). Traditioal Chiese medicie, developed thousads of years ago, ad recorded acupucture texts writte more tha 2,500 years ago are based o the belief that the body has a system of meridias through which eergy (Qi) flows (Cohe & Doer, 96). Symptoms such as ausea are a result of deficiecy of Qi, stagatio (excess) of Qi, or disharmoy of the Qi of the splee ad stomach. The goal of Chiese medicie is to restore the body to a state of eergy balace. Acupressure is oe techique that has bee used to achieve that goal (Gottlieb, 95). Acupressure devices (i.e., wrist bads, travel bads, acupressure bads) have bee developed to provide passive acupressure o P6. Acupressure ca be admiistered by healthcare providers, family members, or patiets themselves (Gottlieb; Porkert & Ullma, 88) ad does ot ivolve pucture of the ski. Because CINV cotiues to be problematic for wome udergoig chemotherapy ad o large trials have bee performed to determie the utility of digital acupressure therapy i wome beig treated for breast cacer, the specific aim of the preset radomized cliical trial was to compare the effects of acupressure o the CINV experiece amog three groups of wome udergoig moderate to highly emetogeic chemotherapy for breast cacer. The groups were defied as those receivig (a) active acupressure via digital pressure o the ei gua poits (P6), (b) placebo acupressure via digital pressure o the hou xi poits (SI3), ad (c) usual care oly. The differeces i axiety ad fuctioal status amog group participats also were measured. Methods The desig for the curret study was a multiceter, logitudial radomized cliical trial throughout oe cycle of chemotherapy. The settigs icluded commuity cliical ocology programs associated with the Uiversity of Texas M.D. Aderso Cacer Ceter i Housto, T, ad ie idepedet sites located throughout the Uited States. The iclusio criteria were wome who were receivig cyclophosphamide with or without 5-fluorouracil, doxorubici with paclitaxel or docetaxel, or 5-fluorouracil, epirubici, ad cyclophosphamide for the treatmet of breast cacer; had a ausea itesity score with previous chemotherapy of at least 3 (moderate) o the Morrow Assessmet of Nausea ad Emesis measurig the worst ausea; were begiig their secod or third cycle of chemotherapy; had the ability to commuicate (verbally ad i writig) i Eglish; ad were willig to participate i the study. Figure 1 details the iductio ad radomizatio schema. Istrumets A patiet iformatio questioaire was used to collect demographic iformatio upo etry ito the study, icludig age, geder, marital status, ethicity, employmet status, icome, ad ausea history. A disease ad treatmet questioaire was used to record iformatio from the medical record, icludig diagostic iformatio, treatmet regime, chemotherapy dosages, ad atiemetics ordered for use at home ad i the chemotherapy site. A daily log cosisted of the three-item ausea experiece subscale of the Rhodes Idex of Nausea (RIN) ad the oe item from the vomitig subscale from Rhodes Idex of Nausea, Vomitig, ad Retchig. The scale has established reliability ad validity (Rhodes & McDaiel, 97; Rhodes, Watso, & Johso, 84; Rhodes, Watso, Johso, Madse, & Beck, 87). Items from the subscales were summed, ad subscale scores could rage from 0 12, with a higher umber reflectig a more severe ausea experiece. I additio, ausea itesity was rated usig a descriptive, umeric ratig scale (NRS) ragig from 0 (o ausea) to (worst ausea imagiable). Participats also were asked to rate their activities (fuctioal status) over the previous 24 hours usig a descriptive NRS ragig from 0 (oe) to (all). 256 eligible patiets 160 erolled 96 refused (60 ot iterested, too busy, too sick, 6 already seeig a acupucturist) Usual care oly group = 54 P6 group = 53 SI3 (placebo) group = completed 3 withdrew completed 6 withdrew 49 completed 4 withdrew Figure 1. Radomizatio Schema 8

3 Self-ratigs were doe o a daily basis, prior to bedtime. The correlatios betwee the three-item RIN ad the sigle-item NRS were from for every measuremet. The reliability of the RIN was 0.92 for the sample. The daily log also provided a place for each perso to record ay itervetios used for ausea ad vomitig cotrol, as well as how ofte acupressure was used to cotrol ausea (for wome i the acupressure groups). The State-Trait Axiety Ivetory of the State Axiety Scale developed by Spielberger (83) is a widely used axiety scale i the Uited States (Naughto, Shumaker, Aderso, & Czaijkowski, 96). The State Axiety Scale cotais 20 items scored o four-poit scales measurig apprehesio, tesio, ad ervousess accordig to how the respoder feels at a particular momet i time. State axiety is defied as a idividual s trasitory emotioal resposes to a stressful situatio such as the admiistratio of chemotherapy. To score the istrumet, the resposes are summed. Higher scores idicate more state axiety (Spielberger). Estimates of the alpha coefficiet of iteral cosistecy have raged from (Spielberger). The validity evidece for the State Axiety Scale is quite strog ad shows discrimiatio i severity levels (Naughto et al.). The reliability was 0.95 i the curret study s sample. Acupressure Itervetio The acupressure treatmet for ausea cosisted of applyig digital pressure to oe of the ei gua poits (P6) located o both forearms (see Figure 2) usig the thumb of the opposite had. If the woma desired, ik marks were applied to her arms to make the P6 poits easier to locate. The poits are held with a depth of pressure described by the recipiet as comfortable for a maximum of three miutes (Gach, 90). Nausea ca make the acupressure poit at P6 teder to the touch. Whe the poit is o loger teder, the treatmet is complete (i.e., the poit has bee released). Sometimes a muscle twitch, a rhythmic throb, a spotaeous yaw, or deep sigh accompaies the release. If the release happes prior to the three-miute mark, the participat may move o to the other poit or cotiue what she was doig prior to experiecig ausea. Participats were istructed to fid a quiet place each morig to perform the acupressure treatmet to both P6 poits sequetially as either treatmet or practice. Durig the Study poit P6 Placebo poit SI3 Figure 2. Acupressure Poits Used i This Study Note. Illustratios courtesy of Acuxo. Reprited with permissio. day, participats i the acupressure groups were ecouraged to use digital acupressure to oe of the poits wheever ausea occurred regardless of where they were. Each acupressure sessio should take approximately six miutes i the morig ad three miutes each durig the rest of the day, depedig o the itesity of the ausea. Participats i the placebo group received the same istructio. A active placebo poit was chose because the researchers were cocered that the teachig ad experiece of acupressure would ot be similar with a sham (oactive) poit. The hou xi poit (SI3, a poit o the ular side of the had), was chose because activatio of that had poit would ot affect ausea treatmet ad the poit is close, but ot too close, to the active P6 poit. Procedures Each istitutio that participated i the study received approval for the protocol from its istitutioal review board. Potetial participats were approached about the study by research assistats, their urses, or their physicias. Each of the research assistats ad urses actig as research assistats received at least two hours of traiig i the study protocol. They also had o-site access to a teachig video about the protocol. After providig coset, each woma completed the baselie data collectio, which icluded the demographic ad axiety measures. Participats were radomized to receive acupressure via digital pressure to P6 plus usual care, placebo digital acupressure to SI3 plus usual care, or usual care oly. Oe of the research assistats taught participats i the acupressure groups how to use the actual or placebo acupressure poits. Participats were taught acupressure i a private room or a examiatio room immediately prior to receivig chemotherapy. The researchers edeavored to keep the research assistat masked as to the active poit. Patiets were coached util they could satisfactorily demostrate to the research assistat how to fid ad apply acupressure to each poit (active or placebo). The wome i the acupressure groups completed a daily log about acupressure usage as well as medicatios take to cotrol their ausea. The daily log was similar to the oe that the usual-care group used. All participats were asked to record ay itervetios they attempted i a effort to cotrol ausea ad were istructed to complete the daily log each eveig for approximately three weeks util their ext cycle of chemotherapy. All participats were called or see o day 8 of the chemotherapy cycle so that ay questios could be aswered, they could be ecouraged to complete the log, ad they could be coached (i.e., the acupressure groups) about the importace of their participatio i the study. A few days before the ext cycle of chemotherapy, a research assistat called all participats to remid them to brig their daily logs to the appoitmet. At the appoitmet, a research assistat collected the daily logs ad asked patiets to complete a exit questioaire, which icluded the axiety measure. The total time required for the participats study ivolvemet was approximately four hours over oe moth. All participats received reimbursemet for parkig durig the extra time required for study participatio. All wome received atiemetic therapy to be used at home as prescribed by their physicias. They were asked to record what they actually took o a daily basis i the log. Although the usual treatmet of ausea varies by patiet, practitioer, 8

4 geographic area, ad isurace coverage, the added value of acupressure was studied i the cotext of usual cliical ausea care. Data Aalysis SPSS for Widows release (SPSS Ic.) ad SAS PROC GLIMMI versio (SAS Istitute, Ic.) software were used for data aalysis. Data were double etered ito SPSS, ad discrepacies betwee files were resolved to esure accuracy of the data etered. Descriptive statistics were geerated for sample characteristics ad other variables of iterest. Aalyses were performed based o the itet to treat philosophy (Piatadosi, 2005). Age was dichotomized to youger tha 55 years ad 55 years or older for some aalyses. HLM 6 versio 6.02 (Scietific Software Iteratioal) software was used to cofirm the results from some SAS software aalyses. Hierarchical geeralized liear mixed-models aalyses (Goldstei, 2003; Raudebush & Bryk, 2002) were coducted with SAS PROC GLIMMI to predict chages i outcomes over the -day post-treatmet period. Multilevel Poisso regressios with overdispersio were used to examie quatitative outcomes whe the distributio of the data clearly was sigificatly skewed. Multilevel logistic regressio was used to examie biary outcomes, adjustig for overdispersio because of the relatively low icidece of the target outcomes. For both methods of aalysis, radom itercept models were estimated with subject-specific, maximum pseudo-likelihood (SAS Istitute, 2004). Mea substitutio ad last value carried forward were used for missig data. Last value carried forward was used oly whe participats clearly experieced o further ausea or vomitig. Whe the wome felt better, missig data became problematic. Results Demographics The participats (N = 160) were, o average, aged 49.3 years ( = 9.4), Caucasia (79), married or partered (74), employed (51), bor U.S. citizes (94), heterosexual (95), ad livig with someoe (92). The average duratio of educatio for the wome was.4 years ( = 2.6); 70 had more tha a high school educatio. The average body mass idex was 27.5 kg/m 2 ( = 5.9 kg/m 2 ). Eighty-oe percet of the participats experieced at least some degree of morig sickess with a pregacy, 36 had a history of seasickess, 34 had a history of beig carsick, ad 28 had a history of ausea with stress. No sigificat differeces i the demographic variables were foud by group assigmet (see Table 1). No sigificat differeces existed amog the groups i the disease ad treatmet variables (see Table 2). Most (76) of the wome were receivig a athracyclie ad cyclophosphamide as their chemotherapy regime. The average dose of doxorubici ( = 5) was 1 mg, ad the average dose of cyclophosphamide ( = 4) was 1,121 mg. The most commo IV atiemetics give durig chemotherapy admiistratio were dexamethasoe (80), odasetro (49), graisetro (24), ad dolasetro (). A variety of combiatios ad dosages of the medicatios were give before ad followig chemotherapy. The most commo atiemetics ordered for home use were prochlorperazie (70), ad 74 had at least oe of the selective atagoists of the serotoi receptor subtype, 5-HT 3, ordered. Fifty-five differet home pharmaceutical regimes were take by the trial participats. Nopharmacologic itervetios icluded exercise, fresh air, Table 1. Demographics by Group Assigmet Usual Care Oly (N = 54) P6 Itervetio (N = 53) SI3 Itervetio (N = 53) Characteristic Age (years) Educatio (years) Body mass idex (kg/m 2 ) Characteristic Employmet Employed Uemployed Ethicity Caucasia Other Bor U.S. citize Relatioship status Married or partered Other Heterosexual orietatio Lives aloe History of car sickess History of seasickess History of morig sickess (N = 137) History of ausea with stress Note. Participats did ot aswer all questios, resultig i missig data. Percetages are based o the umber of actual resposes. 816

5 Table 2. Treatmet Characteristics by Group Assigmet Usual Care Oly (N = 54) P6 Itervetio (N = 53) SI3 Itervetio (N = 53) Characteristic Number of positive odes Dose of cyclophosphamide (mg) Dose of doxorubici (mg) 1, ,043.00, , ,216.00, , ,2.00, Characteristic Breast surgery Lumpectomy Mastectomy Lumpectomy ad mastectomy Bilateral mastectomy Diagosis Ductal Others Nodal surgery Noe Axillary ode dissectio Setiel Both Radiatio therapy No Yes Plaed after chemotherapy Chemotherapy Cyclophosphamide ad athracyclie Other combiatios Note. Participats did ot aswer all questios, resultig i missig data. Percetages are based o the umber of actual resposes. visualizatio, dry toast, crackers, peppermit tea, giger tea, a spooful of hoey, avoidig smells, aromatherapy, avoidig stress, prayer, ad just edurig. Acute Nausea ad Vomitig: Day of Chemotherapy, Study Day 1 I the iitial hours followig chemotherapy admiistratio, emesis was documeted i the logs of less tha ( = 12) of the sample ( = 124). Six wome vomited three times or more. Ufortuately, 36 wome did ot complete their logs ad the reaso for the missig data is ukow. No sigificat differeces i acute emesis were foud by age (c 2 = 1., p = 0.29) or treatmet group (c 2 = 0.67, p = 0.71). Acute ausea occurred more frequetly, with more tha 75 of the wome ( = 94) reportig some ausea, but o sigificat differece i the icidece (dichotomous variable) of ausea was foud by treatmet group (RIN: c 2 = 1., p = 0.55; NRS: c 2 = 1.23, p = 0.55). A sigificat differece did exist for patiet age (RIN: c 2 = 12.87, p < ; NRS: c 2 = 13.61, p < ), with youger wome reportig more acute ausea. Further aalyses idicated that the itesity of ausea raged from 1 o the NRS ( = 4.53, = 2.70) ad 1 12 o the RIN ( = 5.54, = 2.93). The two measures correlated sigificatly at A sigificat relatioship was foud betwee the itesity of acute ausea ad age usig both of the ratig scales (RIN: r = 0.34, p < 0.001; NRS: r = 0.28, p = 0.002), with youger wome reportig a greater itesity of ausea. However, o sigificat differece existed i the itesity of acute ausea by treatmet group usig both ratig scales (RIN: F = 0.607, p = 0.5; NRS: F = 0.550, p = 0.579). After cotrollig for age, o sigificat differeces were foud i the itesity of acute ausea usig either ratig scale (RIN: F = 0.550, p = 0.578; NRS: F = 0.4, p = 0.841). Baselie state axiety was ot sigificatly associated with the icidece or itesity of acute ausea or vomitig. A history of morig sickess, car sickess, or seasickess was ot sigificatly associated with acute ausea or vomitig. A history of ausea with stress was sigificatly associated with acute ausea (c 2 = 6.26, p = 0.012) but ot acute vomitig (p = 0.676). Acute ausea was sigificatly associated with acute vomitig (Spearma rak correlatios: RIN: r s = 0.31, p < ; NRS: r s = 0.32, p < ). Delayed Emesis: Study Days 2 11 For 58 of the sample, delayed emesis did ot occur. Two wome reported that they experieced daily emesis for the -day measuremet period. Of the three patiets who took aprepitat, oe had o vomitig, oe had oe episode o the sixth day, ad oe vomited every day for days. Of the 22 wome who vomited o a sigle day after their chemotherapy, 9 (22) experieced emesis the day after chemotherapy admiistratio, 2 (9) had their first ad oly emesis o day 7, ad the remaiig 11 varied i their patters of vomitig. Takig dexamethasoe (43) or a serotoi (5-HT 3 ) atagoist (dolasetro, graisetro, or odasetro) (74) at home was ot associated with delayed vomitig. A sigificat relatioship 8

6 existed betwee delayed vomitig ad age (t = 3.22, p = 0.002), with youger wome reportig more vomitig. A iitial aalysis of ay (versus o) emesis i the days followig treatmet showed that vomitig was reported o 11 of the days. Emesis was reported o 3 of the 1,3 patiet days. All wome reported a declie i emesis across the days after chemotherapy (t = 6.78, p < ). Of particular iterest was whether wome who used acupressure reported a greater declie i their rate of emesis compared to the placebo or usual-care groups. Differeces amog the groups for chages i emesis across time were examied with multilevel logistic regressio. The results showed that the declie i the icidece of emesis was greater for the P6 acupressure group tha either the placebo group (t = 3.13, p = 0.002, odds ratio [OR] = 1.3) or the usual-care group (t = 4.81, p < , OR = 1.4). The icidece of emesis declied differetly for youger (< 55 years) compared to older wome (> 55 years), with youger wome reportig emesis more frequetly immediately followig treatmet ad a steeper declie i emesis over time (t = 3.37, p = , OR = 1.3). The older wome reported a lower icidece of emesis over the days. The age-group differece i emesis across time also differed sigificatly for the usual-care group, compared to the P6 acupressure group. Youger wome i the usual-care group differed from youger wome i the P6 acupressure group i delayed vomitig, ad the differece was greater tha the aalogous compariso for older wome (three-way iteractio, group by age by time; t = 4.74, p < , OR = 1.5). The estimated declie i the icidece of emesis across timeby group ad age groupca be see i Figure 3. Delayed Nausea: Study Days 2 11 Niety-eight percet of the wome i the study experieced delayed ausea. Fifty-oe percet reported that their ausea had resolved by the seveth day after their chemotherapy, ad 29 still reported some ausea by the th day after chemotherapy. Figure 4 provides a more complete descriptio Nausea Ratig Time (0 9 = Days 2 11) P6, age < 55 P6, age > 55 Usual care oly, age < 55 Usual care oly, age > 55 SI3, age < 55 SI3, age > Figure 3. Hierarchical Geeralized Liear Model Logistic Regressio With Overdispersio: Delayed Emesis (Biary) o Time by Group by Age of the reported delayed ausea over time. Baselie axiety was sigificatly associated with the itesity of delayed ausea for the first four days after chemotherapy (r = , p < 0.03); more axiety at baselie was associated with more delayed ausea. Fuctioal status was sigificatly egatively associated with the itesity of ausea each day (r = to 0.487, p < 0.001); those with more delayed ausea reported lower fuctioal status. Delayed ausea was evaluated with multilevel Poisso regressio by examiig chage from days Reported declies i ausea were greater for wome i the acupressure group tha for the wome i the usual-care group o RIN scores (t = 2.77, p < 0.006, icidece rate ratio [IRR] = 1.05) ad ausea NRS (t = 2.74, p = 0.006, IRR = 1.05). Chage across time did ot differ betwee the acupressure ad placebo groups for either ausea measure. Youger wome reported steeper declies i ausea tha older wome. The estimates for both ausea scores for older wome were lower across all days, whereas the estimated iitial ratigs for youger wome were higher ad the decreased rapidly over time. The differece betwee youger ad older wome was greater for the acupressure group compared with the placebo ad usualcare groups, with the decrease i estimated ausea ratigs beig steeper for the youger wome i the acupressure group (RIN: acupressure versus usual care, t = 4.56, p < , IRR = 1.11; RIN acupressure versus placebo, t = 2.68, p = 0.008, IRR = 1.07; ausea NRS: acupressure versus usual care, t = 4.43, p < , IRR = 1.11; ausea NRS: acupressure versus placebo, t = 2., p = 0.03, IRR = 1.06). The patter of chage for the ausea NRS is show i Figure 5. Patiet Commets Commets were solicited from patiets about their participatio i the study. For the P6 acupressure group, commets icluded the followig. No medicatio all day! Used acupressure. Nausea oly seems to come o whe my stomach is empty. The acupressure helps. Acupressure seems to help after the third day after treatmet. Not too much withi the first few days whe ausea is right after chemo. The members of the placebo (SI3) acupressure group recorded that acupressure did t ecessarily help me, but maybe it would help someoe else ad aromatherapy helped me much more tha acupressure (peppermit oil). By day 5, oe woma recorded acupressure o help yet. A woma i the usual-care group lameted a few days after her chemotherapy that I wish I was i oe of the other groups i this test! Aother woma was so frustrated by beig i the cotrol group that she leared about P6 ad started usig acupressure for her ext cycle of chemotherapy. She recorded that acupressure ca be extremely effective i reducig chemo-iduced ausea. Discussio This is the first comprehesive U.S. study of digital acupressure at P6 over days followig moderate to highly emetogeic chemotherapy (day 1 [acute], days 2 11 [delayed]). The data suggest that digital acupressure at P6 is a useful adjuct to pharmaceutical itervetios for delayed ausea ad vomitig. Specifically, acupressure may haste time to recovery. May wome recorded the most useful effects whe ausea was mild but oted that the techique was helpful i additio to medicatios eve whe the ausea was severe. The 8

7 Percetage Days After Treatmet Nausea All usual activities Figure 4. Delayed Nausea ad Activities Over Time preset study s fidigs cofirm the results of two small-scale digital acupressure studies of the P6 poit for chemotherapyiduced ausea. The first was the pilot study for the curret trial (Dibble et al., 2000), ad the secod treated 40 patiets i Korea with gastric cacer who were udergoig ipatiet chemotherapy (Shi, Kim, Shi, & Juo, 2004). Neither of the previous studies icluded a placebo acupressure group. The use of a placebo acupressure poit as oe group i the curret study stregthes the hypothesis that the results are ot merely because of a placebo effect. I the preset study, self-delivered placebo acupressure was ot sigificatly differet from the usual-care group i cotrollig CINV. The participats were uable to covice themselves that the placebo acupressure worked to cotrol their ausea over time as their commets demostrated. The desig of the curret study helps to aswer the questio about the placebo respose over time. No statistically sigificat differeces were foud betwee the placebo acupressure group ad the usual-care group over time. The data suggest that future researchers may ot eed to icur the expese of a three-group desig for their studies; a two-group desig should be sufficiet for examiig other types of digital acupressure for symptom maagemet. The results cofirm those of Kiele ad Kiee (96), who reported that the extet ad frequecy of placebo effects as published i most of the literature were gross exaggeratios. Two other measuremet issues have bee clearly idetified ad resolved, to some extet, i the curret studythe legth of time ecessary to follow patiets for ausea ad how to measure ausea over time. The most commo time frame for ausea studies is 120 hours (i.e., five days). However, i this study, 70 of the wome still had ausea 120 hours after receivig chemotherapy ad 30 had ausea at day 11. Perhaps two weeks of follow-up would be appropriate whe future studies examie the effect of a itervetio o chemotherapy-iduced delayed ausea. If the wome i this study are accurate ad acupressure works best o mild ausea, measurig ausea for oly five days might miss the importace of acupressure effects as a adjuct to pharmaceutical treatmets that usually are ot ordered beyod five days. The secod measuremet issue is the recordig of the presece ad itesity of ausea or vomitig. The Rhodes Idex of Nausea, Vomitig, ad Retchig is a reliable ad valid istrumet, but it is too legthy for daily use. The NRS used i the curret study was highly correlated ad produced the same fidigs as the RIN. Therefore, the authors would support the use of NRSs for the daily measuremet of ausea ad vomitig. Aother measuremet issue that should be cosidered for future studies of CINV is the iteractio amog age, meopausal status, ad CINV. I this study s data, the researchers were ot able to explore whether the differeces i CINV by age were a fuctio of all of the compoets of agig or just the atural hormoal chages resultig from meopause. Ufortuately, iformatio regardig meopausal status was ot collected. Future research should be desiged to aswer that questio. No study is without limitatios, icludig the curret trial. First, the same research assistats ad urses were teachig the use of both acupressure poits. Although most of them did ot kow which poit was active for the treatmet of ausea, some were quite itet o fidig out ad did so through the Iteret. That issue was true for five patiets. The researchers simply asked all wome to participate i the trial, ad their questios would be aswered after the trial. However, seeig patiets with ausea ad beig a patiet with urelieved ausea ca ad did result i some wome breakig the blid. A few participats had difficulty fidig the poits cosistetly, so the itervetio dosage varied, ad two participats had log figerails that iterfered with performig acupressure. The researchers suggested that the wome use the eraser ed of a pecil to apply the acupressure. This study should be replicated i future research efforts ad coducted with me, childre, ad wome experiecig CINV from other chemotherapeutic agets. Implicatios for Ocology Nurses At least two studies about acupressure have cocluded that acupressure is a importat adjuct to pharmaceuticals i maagig CINV (Dibble et al., 2000; Shi et al., 2004). Those studies as well as the curret study suggest that ocology cliicias ca iclude acupressure i their list of optios for the maagemet of CINV, especially delayed ausea ad Delayed Emesis Time (0 9 = Days 2 11) P6, age < 55 P6, age > 55 Usual care oly, age < 55 Usual care oly, age > 55 SI3, age < 55 SI3, age > 55 Figure 5. Hierarchical Geeralized Liear Model Poisso Regressio With Overdispersio: Delayed Nausea o Time by Group by Age 8

8 vomitig. Traiig i the appropriate techique is straightforward ad easy to obtai through a Chiese medicie provider, a acupucturist, or a massage therapist. Iteret resources also are available (e.g., CINV still is a sigificat problem for may patiets. Specific recommedatios provided by ocology urses are ot oly useful but also are very appreciated by patiets. The authors gratefully ackowledge Research Assistat Stacey Carter, the M.D. Aderso Commuity Cliical Ocology Program uder the directio of Michael Fisch, MD, ad, of course, the participats who made this study possible. Author Cotact: Suzae L. Dibble, DNSc, RN, ca be reached at sue.dibble@gmail.com, with copy to editor at ONFEditor@os.org. Refereces America Cacer Society. (2007). Cacer facts ad fi gures, Atlata, GA: Author. Carr, B., Bertrad, M., Browig, S., Doroshow, J.H., Presat, C., Puloe, B., et al. (85). A compariso of the atiemetic efficacy of prochlorperazie ad metoclopramide for the treatmet of cisplati-iduced emesis: A prospective, radomized, double-blid study. Joural of Cliical Ocology, 3, Cohe, M.R., & Doer, K. (96). The Chiese way to healig: May paths to wholeess. New York: Berkley Publishig Group. Craze, R., & Fou, J.T. (98). Traditioal Chiese medicie. Chicago: NTC Publishig Group. Dibble, S.L., Casey, K., Nussey, B., Israel, J., & Luce, J. (2004). Chemotherapyiduced vomitig i wome treated for breast cacer. Ocology Nursig Forum, 31, E1 E8. Dibble, S.L., Chapma, J., Mack, K.A., & Shih, A. (2000). Acupressure for ausea: Results of a pilot study. Ocology Nursig Forum, 27, 41. Dibble, S.L., Israel, J., Nussey, B., Casey, K., & Luce, J. (2003). Delayed chemotherapy-iduced ausea i wome treated for breast cacer. Ocology Nursig Forum, 30, E40 E. Dudee, J.W., & Yag, J. (90). Prologatio of the atiemetic actio of P6 acupucture by acupressure i patiets havig cacer chemotherapy. Joural of the Royal Society of Medicie, 83, Ezzo, J.M., Richardso, M.A., Vickers, A., Alle, C., Dibble, S.L., Issell, B.F., et al. (2006). Acupucture-poit stimulatio for chemotherapy-iduced ausea or vomitig. Cochrae Database of Systematic Reviews,, CD Gach, M.R. (90). Acupressure s potet poits: A guide to self-care for commo ailmets. New York: Batam Books. Goldstei, H. (2003). Multilevel statistical models (3rd ed.). Lodo: Edward Arold Publishers. Gottlieb, B. (Ed.). (95). New choices i atural healig. Emmaus, PA: Rodale Press. Kiele, G., & Kiee, H. (96). Placebo effect ad placebo cocept: A critical methodological ad coceptual aalysis of reports o the magitude of the placebo effect. Alterative Therapies i Health ad Medicie, 2(6), Naughto, M.J., Shumaker, S.A., Aderso, R.T., & Czaijkowski, S.M. (96). Psychological aspects of health-related quality of life measuremet: Tests ad scales. I B. Spilker (Ed.), Quality of life ad pharmacoecoomics i cliical trials (2d ed., pp ). Philadelphia: Lippicott-Rave. Piatadosi, S. (2005). Cliical trials: A methodologic perspective (2d ed.). Hoboke, NJ: Joh Wiley ad Sos. Porkert, M., & Ullma, C. (88). Chiese medicie. New York: William Morrow. Raudebush, S.W., & Bryk, A.S. (2002). Hierarchical liear models: Applicatios ad data aalysis methods (2d ed.). Thousad Oaks, CA: Sage. Rhodes, V.A., & McDaiel, R.W. (97). Measurig ausea, vomitig, ad retchig. I M. Frak-Stromborg & S.J. Olse (Eds.), Istrumets for cliical health-care research (2d ed., pp ). Sudbury, MA: Joes ad Bartlett. Rhodes, V.A., Watso, P.M., & Johso, M.H. (84). Developmet of reliable ad valid measures of ausea ad vomitig. Cacer Nursig, 7, Rhodes, V.A., Watso, P.M., Johso, M.H., Madse, R.W., & Beck, N.C. (87). Patters of ausea, vomitig, ad distress i patiets receivig atieoplastic drug protocols. Ocology Nursig Forum, (4), SAS Istitute, Ic. (2004). The GLIMMI procedure. Cary, NC: Author. Shi, Y.H., Kim, T.I., Shi, M.S., & Juo, H. (2004). Effect of acupressure o ausea ad vomitig durig chemotherapy cycle for Korea postoperative stomach cacer patiets. Cacer Nursig, 27, Spielberger, C.D. (83). Maual for the State-Trait Axiety Ivetory (form Y). Palo Alto, CA: Cosultig Psychologists Press. Staard, D. (89). Pressure prevets ausea. Nursig Times, 85(4),

9