Research in Nursing & Health, 1991, 14. 249-257

Comparison of Patient-Controlled and Nurse-Controlled Antiemetic Therapy in Patients Receiving Chemotherapy Jody Nerhood Edwards, JoAnne Herman, Beth Kraley Wallace, Michael D. Pavy, and Joan Harrison-Pavy

The purpose of this quasi-experimental pilot study was to compare the effect of patientcontrolled (PCAE) and nurse administered (NCAE) antiemetic therapy for controlling chemotherapy-induced nausea and vomiting in patients receiving moderate emetogenic chemotherapy. Twenty subjects were randomly assigned to either the PCAE group who received I V antiemetic medication via a patient-controlled pump or the NCAE group who received antiemetic medication via nurse administered minibags. Nausea, vomiting, sedation, and drug consumption were measured. There was no difference in nausea scores between the two groups. Subjects in the PCAE group consumed significantly less medication than subjects in the NCAE group.

Chemotherapy-induced nausea and vomiting are common and distressing side effects to patients (Clark, Tyson, Gralla, & Kris, 1989; Durant, 1984; Grant, 1987; Marrow, 1989; Rhodes, 1988; Rhodes & Watson, 1987; Rhodes, Watson, Johnson, Madsen, &Beck, 1989; Wickham, 1989). Methods to reduce or prevent nausea and vomiting have been identified as priorities for cancer nursing research (Dodd, 1987; Funkhouser & Grant, 1989; Western Consortium for Cancer Nursing Research, 1987). Physiological complications of nausea and vomiting include electrolyte imbalances (Clark et a]., 1989; Rhodes, Watson, Johnson, Madsen, & Beck, 1987; Wickham, 1989), changes in immune status (Grant, 1987), aspiration pneumonia (Johnson & Gross, 1985), and physical trauma such as Mallory-Weiss tears of the esophagus (Wickham, 1989) and pathological fractures (Whitehead, 1975). Nausea and vomiting also produce psychological sequelae such as anticipatory nausea and vomiting

(Clark et al., 1989; Duigon, 1986; Grant, 1987; Wickham, 1989) and prevention of cure (Grant, 1987; Rhodes et al., 1989; Wickham, 1989). Some patients feel the treatment and the probability of cure may no&be worth the side effects experienced. In addition, physicians, in a misguided attempt to prevent or alleviate nausea and vomiting, may administer subtherapeutic doses of chemotherapy (Durant, 1984). A variety of physiological trigger sites have been identified which impact on the development of nausea and vomiting (Flaherty, 1985; Grant, 1987; Wickham, 1989; Yasko, 1985). The emetic or true vomiting center (EC), located in the medulla oblongata, receives impulses via neurotransmitters from five areas: chemoreceptor trigger zone, cerebral cortex and limbic system, vestibulocerebellar afferents, vagal visceral afferents, and sympathetic visceral afferents in the gastrointestinal tract. Each of these areas is sensitive to certain emetic stimulating substances or events (Yasko, 1985). Since

Jody Nerhood Edwards, MS, RN, C, OCN, is a clinical nurse specialist; Beth Kraley Wallace, RPh, is a staff pharmacist; Michael D. Pavy, MD, is medical director of the Cancer Program; and Joan Harrison-Pavy, MN, RN, is director of the Cancer Program, all at McLeod Regional Medical Center, Florence, SC. JoAnne Herman, PhD, RN, is an associate professor at the College of Nursing, University of South Carolina, Columbia, SC. This work was supported in part by a Summer Research Grant, American Cancer Society, South Carolina Division; BARD MedSystems Division of C.R. BARD, Inc.; and by an American Cancer Society scholarship in Cancer Nursing awarded to Jody Edwards. This article was received on June 28, 1990, was revised, and accepted for publication December 11, 1990. Requests for reprints can be addressed to Or. JoAnne Herman, University of South Carolina, College of Nursing, Columbia, SC 29208.

0 1991 John Wiley & Sons, Inc. 0160-6891191/040249-09 $04.00

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there are multiple pathways for stimulation of the EC, it follows that drug combinations are more effective than single agents in controlling nausea and vomiting that occur as a result of chemotherapy (Clark et al., 1989; Kris, Gralla, Clark, Tyson, & Groshen, 1987; Wickham, 1989; Yasko, 1985). In addition to multiple drug combinations, behavioral strategies such as rational emotive therapy, cognitive reappraisal, guided imagery (Grant, 1987; Frank, 1985), and progressive relaxation (Cotanch, 1989;Cotanch & Strum, 1987) have shown promise as interventions for the prevention and control of chemotherapy-induced nausea and vomiting. Recently, Pelletier and Herzing (1988) proposed that cognitive control is an important factor in an individual’s self-regulation of physiological and psychological status. The patient-controlled analgesia pump (PCA) for the delivery of antiemetic therapy is one potentially useful strategy that combines the efficacy of multiagent antiemetics with the added dimension of patient control. The PCA pump is a patientactivated/nurse-programmed intravenous drug delivery system which provides for lower, more frequent dosing immediately upon the patient’s request (Bard MedSystems Division, 1987). Advantages of PCA therapy for the administration of narcotics include a hierarchy of pharmacological effect resulting in greater analgesia with less drug, less sedation (Kane, Lehman, Dugger, Hansen, & Jackson, 1988), a decrease in unnecessary screening activities, and a decrease in the potential for overdosage (Gaysek, 1987; Jacobsen, 1989; Lange, Dahn, &Jacobs, 1988; Wermeling, Foster, Rapp, & Kenady, 1987). In a very recent study, Hill and associates (1990) found bone marrow transplant patients required less morphine when administered with a PCA pump than with continuous infusion. However, they found no difference in sedation side effects. In summary, a patientcontrolled drug delivery pump using narcotic analgesics provides pain relief with less medication and fewer side effects. “Nausea has many parallels with pain” (Cotanch, 1989, p. 246). Both are symptoms, are self-limiting in nature, and are difficult to assess. Antiemetics parallel analgesics in that sedation is their principal side effect (Cotanch, 1989; Grant, 1987; Wickham, 1989). The application of the PCA concept to antiemetic therapy is proposed to produce a similar reduction in sedation side effects. Therefore, it is postulated that antiemetic drugs administered via a PCA pump (PCAE) will provide nausea and vomiting control with a corresponding reduction in amount of drug consumed and incidence of

side effects in patients receiving chemotherapy. In addition, the PCA pump may augment the effect of the medication through the mechanism of patient control. Before testing the effect of control on nausea and vomiting, it was necessary to determine if the pump could be used successfully to control post chemotherapy nausea and vomiting in cancer patients. The following hypotheses were tested: 1. Subjects receiving antiemetic therapy via a patient-controlled pump (PCAE) will report the same amount of nausea as subjects receiving antiemetic therapy via minibags administered by the nurse (NCAE) when measured l hr, 12 hr, and 24 hr following moderate emetic potential chemotherapy. 2. Subjects receiving antiemetic therapy via a patient-controlled pump will experience the same amount of vomiting as subjects receiving antiemetic therapy via minibags administered by the nurse when measured 1 hr. 12 hr, and 24 hr following moderate emetic potential c hernotherapy . 3. Subjects receiving metoclopramide (Reglan) antiemetic therapy via a patient-controlled pump will consume less medication than subjects receiving Reglan antiemetic therapy via minibags administered by the nurse when measured 1 hr, 12 hr, and 24 hr following moderate emetic potential chemotherapy. 4. Subjects receiving diphenhydramine (Benadryl) antiemetic therapy via a patient-controlled pump will consume less medication than subjects receiving Benadryl antiemetic therapy via minibags administered by the nurse when measured 1 hr, 12 hr, and 24 hr following moderate emetic potential chemotherapy. 5 . Subjects receiving antiemetic therapy via a patient-controlled pump will experience less sedation than subjects receiving antiemetic therapy via minibags administered by the nurse when measured 1 hr, 12 hr, and 24 hr following moderate emetic potential chemotherapy.

METHOD A posttest only, double blind, control group design was used in this quasi-experimental pilot study. Subjects were randomly assigned to either the control group (NCAE) or the experimental group (PCAE). The nurse administering the antiemetic therapy, the patient receiving the antiemetic therapy, and the data collectors were not aware of group assignment.

PCA ANTIEMETIC THERAPY

Sample The sample consisted of 20 subjects over the age of 18 who had been admitted to the 21-bed inpatient unit of a 325-bed regional medical center in the Southeastern United States. All subjects had a definitive diagnosis of cancer, had no known allergies to the antiemetic drugs, and were receiving chemotherapy drugs for the first time. All subjects received moderately emetogenic intravenous chemotherapy. Moderate emetic potential drugs were defined as those identified by two of three references as exhibiting moderate emetic potential (Hogan, 1983; Oncology Research Center, 1985; Steel, 1982). Cyclophosphamide, either alone or in combination, was the most commonly administered chemotherapy drug. Six subjects received cyclophosphamide only, 3 received cyclophosphamide with doxorubicin, 3 received cyclophosphamide with etoposide, and 2 received cyclophosphamide with doxorubicin and fluorouracil. Cyclophosphamide with vincristine, methotrexate, carmustine, cyclophosphamide with vincristine and carmustine, cyclophosphamide with etoposide and doxorubicin, and cytarabine with daunomycin each were administered to 1 subject. Inpatients were chosen for two reasons. First. the patient-controlled pump had never been used to deliver antiemetic drugs and its efficacy was unknown; close supervision by health care professionals seemed prudent. Second, the researchers wanted a double-blind design so that the effect of the pump administration technique could be separated from the influence of control and the placebo effect. The double-blind design would not have been possible in the outpatient setting. Potential subjects who had a prior history of gasmc cancer or major gastrointestinal illness were excluded from the study to avoid confounding the measurement of nausea and vomiting. Patients with psychiatric illness or mental retardation were excluded because of their inability to give informed consent and/or comprehend the instructions for the use of the pump. Of the 20 subjects, 9 were in the PCAE group and 1 1 were in the NCAE group. Subjects in the PCAE group had a mean age of 59.5 years with a range of 46 to 72 years. Five of the subjects were women and 4 were men. The majority (6) were Caucasian. Similarly, the mean age of the subjects in the NCAE group was 58.2 years with a range of 19 to 81. Six of the subjects were women and 5 were men. The majority (9) were Caucasian. A wide variety of cancer diagnoses existed among the sample. Four of the subjects, all in the NCAE group, were diagnosed

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with leukemia. Four subjects in the NCAE group and 2 subjects in the PCAE group had small cell cancer of the lung. One subject in the NCAE group and 2 in the PCAE group had multiple myeloma. One subject in the NCAE group and 2 in the PCAE group were diagnosed with breast cancer. The remaining 4 subjects had glioblastoma, ovarian cancer, adenocarcinoma of the colon, and pancreatic cancer.

Instruments Nausea was measured using a self-report, 1 -item visual analogue scale (NS). This technique was chosen because it is easy for subjects to understand, simple to administer, and accurately measures symptom intensity (Gift, 1989). Since nausea is a subjective sensation discernible only to the patient, self-report is the appropriate measurement technique (Rhodes & Watson, 1987). The visual analogue scale eliminates the confusion caused by the use of adjectives to represent intensity of sensations and reduces the cognitive energy required to complete the data collection instrument (Gift, 1989). The visual analogue scale consisted of a 100mm horizontal line anchored at one end by “not at all nauseated” and at the other end by “extremely nauseated.” Each subject’s score was determined by measuring the distance from the end of the line marked “not at all nauseated” to the slash mark placed by the subject on the line. Potential scores ranged from 0 to 100. Test-retest reliability for the NS has been established by Fetting, Grochow, Folstein, Ettinger, and Colvin (1982), who found a correlation of .83 between two measurement periods separated by 10 to 15 min. Vomiting (VS) was measured by patient report and nurse observation using a researcher-generated instrument which was adapted from the ECOG Recommendations for Grading Acute and Subacute Toxicities (Steel, 1982). The tool was designed to categorize the number of vomiting episodes and included all retching with and without emesis. The tool consisted of a 5-point Likert scale with the points labeled from 0 to 4. Zero was defined as no emesis, while 1 indicated less than 5 retches with or without emesis, 2 = 5 to 9 retches with or without emesis, 3 = 10 to 15 retches with or without emesis, and 4 = intractable vomiting. Staff nurses on the oncology unit were instructed in the use of the VS and rated the subjects. Interrater reliability for the VS was determined by having the staff nurses and researcher rate two subjects.

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This procedure produced 80 pairs of scores for vomiting. The correlation coefficient was .79 (Edwards, 1988). Sedation level (SLS) also was measured with nurse observation using a researcher generated tool adapted from the Abbott Laboratories PatientControlled Analgesia Flow Sheet (1985). The tool consisted of a 5-point Likert scale with the points labeled from 0 to 4. Zero was defined as wide awake while 1 was drowsy, 2 was dozing or sleeping less than 50% of the time, 3 was sleeping greater than 50% of the time, and 4 was awake only when deliberately aroused. Interrater reliability was determined for the SLS using the procedure previously described for the VS; the correlation coefficient was .83 (Edwards, 1988).

Procedure Approval for the study was obtained from the medical center’s Institutional Review Board. Subjects were assigned by pharmacy staff using random drawing of lots to either the experimental group which received PCAE or the control group which received NCAE. Because pharmacy staff made the group assignments, the researcher was blind to treatment group and the possibility of experimenter bias was substantially reduced. The researcher explained the purpose of the study to patients who met the inclusion criteria, invited them to participate, and requested that they sign a consent form. Next, the researcher provided the subject with a series of verbal instructions about nausea and vomiting and the PCA pump. In order to assure that subjects could provide the needed information, the researcher provided the subjects with synonyms for nausea such as queasy, squeamish, sick to the stomach, and synonyms for vomiting such as retching or throwing up. Each subject received visual and verbal instructions on proper use of the PCA pump. Subjects practiced depressing the button on the pump and heard the sound of pump activation. They were told that this sound indicates the computer has received their request for medication. Subjects were instructed to depress the control button at the first sensation of nausea or vomiting. In addition, subjects were advised of the safety mechanisms built into the pump to prevent accidental overdose. Subjects in both groups received IV lorazepam (Ativan) and dexamethasone (Decadron) given by the nurse prior to chemotherapy. In addition, both groups were premedicated with IV Reglan and Benadryl by either minibag or PCA pump. Fol-

lowing chemotherapy administration, subjects in both groups received IV Decadron which was repeated every 3 hr for 3 doses. After chemotherapy, subjects in the NCAE group received minibags of IV Reglan and Benadryl by a registered nurse on a predetermined schedule. NCAE group minibags contained Reglan 0.4 mgm per kg. of ideal body weight and Benadryl 12.5 mgm in a 50 mL solution of Dextrose 5% in water (D5W). Minibags were administered over 30 min at 3 hr intervals for a total of five minibags. NCAE subjects received a placebo of normal saline via the patientcontrolled pump when they depressed the control button. Subjects in the PCAE group received IV bolus injections of Reglan and Benadryl from the patient-controlled pump when they depressed the button. PCAE group injections contained 9.73 mgm of Reglan and 2.65 mgm of Benadryl diluted in 2 ml of D5W. The pump was set with a 15min delay interval. They also received placebo minibags of normal saline via the nurse on the same schedule as the NCAE group. All subjects had nausea, vomiting, and sedation level determined for three intervals. These scoring intervals were from initiation of chemotherapy to Hour 1, from the time of the first measurement to Hour 12, and from the second measurement to Hour 24. Nausea was measured once at the end of each time interval. All instances of retching and/or vomiting that occurred during data collection were recorded. Sedation was measured at the end of each time interval with the nurse rating the patient’s behavior during the entire time interval. Drug consumption was computed by multiplying the mgm per mL of Reglan and Benadryl times the total number of mL consumed during each measurement period.

RESULTS Data were analyzed using a variety of descriptive statistics. The hypotheses were tested using the Mann-Whitney U nonparametric equivalent of the t test. This technique was chosen because the sample was small and some of the data were at the ordinal level of measurement (Gibbons, 1976; SPSSX Users Guide, 1988). The Bonferroni adjustment was applied to control for Type I error during multiple comparisons (Hinkle, Wiersma, & Jurs, 1979; Volicer, 1984). Therefore, an alpha of .025 rather than .05 was used to determine significance. The subjects experienced mild nausea at all three of the measurement periods indicating that

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both methods of administration of medication provided effective nausea control. The highest possible nausea score was 100. The highest mean score for either group at any of the time periods was 11.2. Only a few subjects scored in the higher range. The mean nausea scores measured in millimeters for both groups and the test of hypothesis 1 are displayed in Table 1. The nausea scores of the two groups were similar. Both groups demonstrated an increase in level of nausea at each time period. However, subjects in the PCAE group reported a larger increase in nausea at Hour 24. Hypothesis 1 was supported indicating that there was no significant difference in nausea scores between the two groups at any of the time intervals. Testing of Hypothesis 2 was not possible because only one subject in the entire sample vomited during the study. Vomiting occurred in the Hour 1 interval postchemotherapy in a subject in the NCAE group. This finding is additional evidence that both methods of medication administration provided antiemetic control. The amount of Reglan and Benadryl consumed by the two groups was substantially different at all measurement intervals. The mean, standard deviation, and range for the drugs are shown in Table 2 . The Mann-Whitney U comparisons of groups at the three time intervals revealed a statistically significant difference in drug consumption between the two groups. Subjects in the PCAE group consumed much less drug than subjects in the NCAE group at Hour 1, Hour 12, and Hour 24. The difference was especially apparent during the Hour 12 measurement interval when the bulk of traditionally administered antiemetics are given. Subjects in the PCAE group used a mean of 14 mgm of Reglan and 3.8 mgm of Benadryl while subjects in the NCAE group used 72 mgm of Reglan and 35.2 mgm of Benadryl. Hypotheses 3 and 4 were supported.

Hypothesis 5 was a prediction that subjects in the PCAE group would experience less sedation than subjects in the NCAE group. Since there was a statistically significant difference in amount of medication consumed by the two groups, it follows that there would be less sedation in subjects in the PCAE group. However, the Mann-Whitney U test revealed no significant differences between groups at Hour 1 or Hour 24 (see Table 3). Unexpectedly, subjects in the PCAE group were more sedated than subjects in the NCAE group at Hour 12 and this difference was statistically significant ( p = .015). While this finding was unexpected, there are some plausible explanations. The Hour 12 measurement interval occurred at night when subjects could be expected to be sleeping. It appears that normal sleeping confounded the measurement of sedation. Close inspection of the mean sedation levels of the two groups at Hour 12 reveals that subjects in the PCAE group scored heavily in the categories that could be described as sound sleeping. It is possible that the PCAE subjects experienced less nausea, were more comfortable and, therefore, were sleeping well. On the other hand, subjects in the NCAE group scored heavier in the category described as sleeping less than 50% of the time. Perhaps these subjects were uncomfortable and their nausea interrupted sleep. An alternative explanation is that the SLS was not a reliable and valid measure of sedation because the category definitions could be interpreted in different ways by the data collectors.

DISCUSSION The purpose of this pilot study was to determine if nurse-administered and patient-controlled antiemetic therapy were equally effective in con-

Table 1. Mann Whitney U Comparison of Nausea Scores Between PCAE and NCAE Groups at Hour 1, Hour 12, and Hour 24 Following Chemotherapy Group Hour 1 PCAE NCAE Hour 12 PCAE NCAE Hour 24

Mean

SO

Range

Mann-Whitney U

P

2.1 4.5

1.8 6.2

0 to 4 0 to 20

40.5

.49

9.9 8.5

20.8 14.2

0 to 64 47.0

.84

0 to 44

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Table 2. Mann Whitney U Comparison of Antiemetic Consumption in Milligrams Between PCAE and NCAE Groups at Hour 1, Hour 12, and Hour 24 Following Chemotherapy Group Reglan Hour 1 PCAE NCAE Hour 12 PCAE NCAE Hour 24 PCAE NCAE Benadryl Hour 1 PCAE NCAE Hour 12 PCAE NCAE Hour 24 PCAE NCAE

P

Mean

SD

Range

Mann-Whitney U

20.5 24.1

3.2 3.6

19 to 29 17 to 29

19

,016

14.1 72.2

28.0

0 to 88 51 to 87

11

,002

0 to 29 17 to 29

11

,002

0