THE PURPOSE of the Research to Practice column is to assist the advanced practice nurse (APN) with the translation of research to practice. For each column, a topic and a particular research study is selected. The stage is set by introducing the importance of the topic using a case-based scenario. The research paper is then reviewed and critiqued, and finally, the implications for translation into practice are discussed. In this column, the following research article is reviewed: Kostic, M. A., Gutierrez, F. J., Rieg, T. S., Moore, T. S., & Gendron, R. T. (2010). A prospective, randomized trial of intravenous prochlorperazine versus subcutaneous sumatriptan in acute migraine therapy in the emergency department. Annals of Emergency Medicine, 56(1), 1–6. The implications of these findings for APNs are discussed.
A 27-year-old woman is being evaluated for a chief complaint of headache for the past 24 hr. Her physical examination findings are unremarkable, neurologic examination is normal, and she has recently undergone a complete headache work-up by the neurology team to include magnetic resonance imaging of the head, which was interpreted by the neuroradiologist as normal for age. She complains of a headache that is 10 out of 10 on the visual analog pain scale. Associated symptoms include photophobia, nausea, and noise intolerance. She was placed in an examination room with the lights off to reduce stimuli associated with worsening of her symptoms. The patient had a prescription for sumatriptan tablets that she did not refill. As the APN coordinating the patient's care you are considering the treatment options.
DESIGN AND METHODS
The authors of the study conducted a double-blind, placebo-controlled, randomized clinical trial to determine whether intravenous (IV) prochlorperazine with diphenhydramine is superior to subcutaneous sumatriptan in the treatment of migraine patients in the emergency department (ED). Using a convenience sample of patients presenting to the ED with a chief complaint of headache and who met criteria for migraine, patients were randomized to receive either the prochlorperazine plus diphenhydramine (active) treatment along with a placebo subcutaneous injection (to mimic administration of sumatriptan), or subcutaneous sumatriptan (active treatment) with a placebo IV injection as control. Pain, sedation, and nausea were all assessed using 100-mm visual analogue scale (VAS), measured at baseline and at 20-min intervals for 80 min or until the patient was discharged from the ED. In addition, telephone follow-up was attempted 72 hr after discharge to assess whether there was any recurrence necessitating an unscheduled return to the ED or other provider.
SAMPLE SIZE AND DATA ANALYSIS
On the basis of a power analysis, the investigators determined they needed a minimum of 62 patients (31 in each arm) to detect a 13-mm difference in scores, the difference defined by the investigators (based on previous studies) as clinically important. Measures were analyzed using standard statistical software packages.
A total of 187 patients presented to the ED with migraine headaches during the study period. Of those, 66 completed the study, 31 in the prochlorperazine group and 35 in the sumatriptan group. The groups were similar in terms of gender, age, baseline pain scores, and other demographic and clinical variables. Although both treatments were effective, patients in the prochlorperazine group reported a greater overall improvement in pain than the sumatriptan group; their pain was relieved more quickly and there was less variability in their responses. The reported pattern of sedation was quite similar between the groups, as was the pattern for nausea. The prochlorperazine group reported less nausea than that of the sumatriptan group, but this finding was not statistically significant. The 72-hr follow-up was successful for 66 (61%) participants, and although participants in the prochlorperazine group reported fewer recurrences of headaches than those in the sumatriptan group, no patients in either group required an unscheduled return to the ED or other provider. Of the 26 patients who were not able to be contacted, none had an unscheduled visit to any provider in the closed health care system in which the study took place.
The authors stated that this is the first reported prospective trial of adult ED patients with migraines that directly compared these two common agents in standard doses. The results showed prochlorperazine as superior to sumatriptan in relieving pain associated with migraine headaches, and although this was not designed as a cost–benefit study, the authors did point out that a single IV injection of 10 mg of prochlorperazine with 12.5 mg of diphenhydramine cost that facility $2.78 compared to the $34.78 for the single subcutaneous injections of sumatriptan. Even with the added cost of the IV materials (estimated at $12.60), the sumatriptan was significantly more expensive. The authors concluded that while both treatments were successful in relieving the presenting migraine headache pain, IV prochlorperazine with diphenhydramine was the superior treatment in this study. One limitation reported in this study was the incomplete follow-up data. However, this study took place in an ED that was part of a closed department of defense network, and it is unlikely that any of the participants would have sought or received care outside of this system.
This is an excellent example of well-designed prospective, randomized, placebo-controlled clinical trial. Using the Joanna Briggs Institute standards for evaluating evidence, this study lies somewhere between a level 1 (the strongest possible evidence of effectiveness) and level 2, which is still considered quite strong (Joanna Briggs Institute, 2011). The reason it is not clearly at the highest level is that it is a single study with a relatively small sample.
The critical components in the design of this study are first, the fact that all parties were blinded to the treatment and controls. The study medications were prepared by the pharmacy to look exactly alike and were not identifiable to the study team. Thus, the nurse administering both the IV and subcutaneous substances did not know which was the active treatment or which was the placebo. Second, patients were randomly assigned to each arm of the study. While the authors do not elaborate on how that was done, the typical scenario is that study packets are assembled by the study team, sealed, randomly assigned an order (usually by a computer program), and kept in the pharmacy. Once a patient has signed the consent form, the pharmacy is notified, the next study packet is pulled, and the pharmacy prepares the substances as directed in that packet. Because neither the physicians nor the nurses get to choose which packet is assigned to which patient, there is no temptation to try to “beat” the system and have a patient purposely assigned to one group or another.
The measures used in this study and the type of analysis also deserve some comment. The authors chose to use a VAS as a means of quantifying patients' subjective experiences of pain, sedation, and nausea. The VAS is similar in some respects to the familiar 1–10 scale that nurses frequently use to assess pain, but it is different in some important ways. The 1–10 scale (or FACES scale) is an ordinal measure, so nurses know that a score of 10 indicates more pain than a score of five, but there is no way to quantify that difference. Although this is sufficient in practice, it limits the kinds of statistical tests that can be done using those measures. A VAS uses a precisely measured line of 100 mm, anchored by the two extremes of the measure, for example, no pain or worst pain imaginable. The subject is asked to place a hash mark on the spot along the line that indicates the current level of pain—or whatever attribute is being measured. The investigator can then measure the difference between the rating at Time 1 and that of Time 2 in terms of millimeters. Figure 1 is an example (not to scale) of a VAS in which the study participant indicates a pain level of approximately 50 mm. For analytic purposes, this effectively turns an ordinal measure into an interval measure and allows the investigator to use more powerful statistical analyses. However, results derived from a VAS should be interpreted cautiously; while sophisticated analyses might yield statistical significance, it is not clear clinically what a millimeter difference in the reported attribute—in this case pain—actually represents (Crichton, 2001).
Lastly, the investigators used an interesting analysis in this study, which made their results highly clinically relevant. They could have done standard statistical tests such as the difference in mean pain scores between groups, but that would not have provided readers with an estimate of the clinical impact of the difference. Instead, they established a definition of clinical significance on the basis of prior research, that is, a 13-mm difference in scores, and then analyzed their data to see if, in fact, there was a clinically significant difference in pain relief, sedation levels, or nausea between the two groups. When looking to translate evidence into practice, it is the clinical impact of the intervention that should serve as the important evidence of effectiveness, and these investigators gave readers that information clearly and concisely.
The research reviewed provides evidence for the use of prochlorperazine with diphenhydramine when compared with sumatriptan for treatment of migraine headache. This is useful information for the APN to consider when caring for the patient experiencing a migraine headache. Management of headaches can be controversial and the evidence provided by these authors provides some clarity for the APN contemplating pharmacologic strategies associated with optimal patient outcomes.
Currently, there is significant attention focused on the standard of care related to the management of migraine headaches in the ED. The Agency for Healthcare Research and Quality is presently evaluating migraine management as part of the effective health care program focused on providing evidence for clinicians caring for specific patient populations such as migraine headache in the ED (Agency for Healthcare Research and Quality, 2011). A draft analytical framework provides treatment options, intermediate and final health outcomes for the patient presenting to the ED with a migraine that will assist the APN in providing the best care.
The research performed by Kostic et al. (2010) provides evidence that can be used within the framework provided by the Agency for Healthcare Research and Quality. The knowledge that the less costly treatment arm resulted in better pain management in this trial than the more expensive treatment arm is important information for the APN. Using fiscally prudent treatment options that are as effective, if not superior to newer options such as triptans, makes sense for the patient and the health care system. Cost per visit is under scrutiny at all levels of the health care industry. Use of the less expensive pharmacologic agents that have equal or superior clinical outcomes can help reduce the cost per visit. The APN can apply the information in the research reviewed to provide excellent, evidence-based care to the patient with a migraine headache.
Agency for Healthcare Research and Quality. (2011). Comparative effectiveness of acute migraine treatments in emergency settings. Effective Health Care Programs. Retrieved from http://www.effectivehealthcare.ahrq.gov/index.cfm/search-for-guides-reviews-and-reports/?pageaction=displaytopic&topicid=289
Crichton N. (2001). Information point: Visual analogue scale (VAS) contained
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Kostic M. A., Gutierrez F. J., Rieg T. S., Moore T. S., Gendron R. T. (2010). A prospective, randomized trial of intravenous prochlorperazine versus subcutaneous sumatriptan in acute migraine therapy in the emergency department. Annals of Emergency Medicine, 56(1), 1–6.