The Journal of Emergency Medicine, Vol. -, No. -, pp. 1–6, 2014 Copyright Ó 2014 Elsevier Inc. Printed in the USA. All rights reserved 0736-4679/$ - see front matter

http://dx.doi.org/10.1016/j.jemermed.2014.02.010

Pharmacology in Emergency Medicine

PREDNISONE FOR EMERGENCY DEPARTMENT LOW BACK PAIN: A RANDOMIZED CONTROLLED TRIAL Barnet Eskin, MD, PHD,* Richard D. Shih, MD,* Frederick W. Fiesseler, DO,* Brian W. Walsh, MD,* John R. Allegra, MD, PHD,* Michael E. Silverman, MD,* Dennis G. Cochrane, MD,* David F. E. Stuhlmiller, MD,† Oliver L. Hung, MD,* Alex Troncoso, MD,* and Diane P. Calello, MD* *Department of Emergency Medicine, Morristown Medical Center, Morristown, New Jersey and †Department of Emergency Medicine, Newton Medical Center, Newton, New Jersey Reprint Address: Barnet Eskin, MD, PHD, Department of Emergency Medicine (Box 8), Morristown Memorial Hospital, 100 Madison Avenue, Morristown, NJ 07962-1965

, Abstract—Background: Although oral corticosteroids are commonly given to emergency department (ED) patients with musculoskeletal low back pain (LBP), there is little evidence of benefit. Objective: To determine if a short course of oral corticosteroids benefits LBP ED patients. Methods: Design: Randomized, double-blind, placebo-controlled trial. Setting: Suburban New Jersey ED with 80,000 annual visits. Participants: 18–55-year-olds with moderately severe musculoskeletal LBP from a bending or twisting injury # 2 days prior to presentation. Exclusion criteria were suspected nonmusculoskeletal etiology, direct trauma, motor deficits, and local occupational medicine program visits. Protocol: At ED discharge, patients were randomized to either 50 mg prednisone daily for 5 days or identicalappearing placebo. Patients were contacted after 5 days to assess pain on a 0–3 scale (none, mild, moderate, severe) as well as functional status. Results: The prednisone and placebo groups had similar demographics and initial and discharge ED pain scales. Of the 79 patients enrolled, 12 (15%) were lost to follow-up, leaving 32 and 35 patients in the prednisone and placebo arms, respectively. At followup, the two arms had similar pain on the 0–3 scale (absolute difference 0.2, 95% confidence interval [CI] 0.2, 0.6) and no statistically significant differences in resuming normal activities, returning to work, or days lost from work. More patients in the prednisone than in the placebo group sought additional medical treatment (40% vs. 18%, respectively, difference 22%, 95% CI 0, 43%). Conclusion: We detected

no benefit from oral corticosteroids in our ED patients with musculoskeletal LBP. Ó 2014 Elsevier Inc. , Keywords—low back pain; steroids; musculoskeletal pain

INTRODUCTION Low back pain (LBP) is a common medical problem with a lifetime incidence well over 50% (1). It accounts for as many as 139 million medical visits a year in the United States (US), of which 2.6 million take place in the emergency department (ED) (2–7). Some researchers distinguish between radicular and musculoskeletal LBP clinically, although there is likely considerable overlap between these entities (7–13). The ED treatment of LBP is predominantly supportive and not particularly effective (7). Most patients receive a combination of nonsteroidal antiinflammatory drugs, opioids, and muscle relaxants (2–6). In addition, approximately 5% receive corticosteroids despite the paucity of data supporting efficacy (6). Further, the evidence supporting this therapy for musculoskeletal, as opposed to radicular, LBP is even less convincing. Corticosteroids are commonly used for other painful and inflammatory conditions and have the

RECEIVED: 15 June 2013; FINAL SUBMISSION RECEIVED: 27 January 2014; ACCEPTED: 10 February 2014 1

2

B. Eskin et al.

advantages of long half-life, inexpensive cost, and diverse administration routes. The objective of this study is to assess the efficacy of oral corticosteroids for the treatment of acute musculoskeletal LBP presenting to an ED. MATERIALS AND METHODS We utilized a prospective randomized controlled study design performed at a suburban ED with an annual patient census of 80,000. All patients from 18 to 55 years of age with a chief complaint of back pain were eligible if the treating emergency physician diagnosed musculoskeletal LBP from a bending or twisting injury within the last 48 h of moderate or greater intensity ($5 on a 10-cm visual analog scale [VAS]). Patients with acute exacerbation of chronic back pain were not excluded. Exclusion criteria were blunt trauma to the lower back, neurological motor deficits of the lower extremities, neoplastic disease, fever, pregnancy, current use of steroids or other immunosuppressive therapy, diabetes, uncontrolled hypertension, significant peptic ulcer disease, cataracts, urinary tract infection, allergy to prednisone, lactose intolerance, visits from a local occupational medicine program, and refusal to participate. Physicians completed a standardized data collection instrument that included demographic, historical, and clinical questions. The treating emergency physician decided on the analgesic therapy in the ED, but this could not include corticosteroids. After enrollment, patients were randomized to the study or placebo group by computer randomization in a double-blind fashion. Allocation to each group was concealed. Those receiving the study medication were given 50 mg of prednisone by mouth and four doses of the same medication to take home (50 mg daily). The placebo group received the same regimen as the study group, using an inactive tablet that was prepared in the hospital pharmacy and was identical in appearance to the prednisone. All study participants, clinicians, and study personnel were blinded to group assignment until all data collection was completed. Patients were discharged home with additional rescue medications, prescribed at the discretion of the treating attending emergency physician. Pain assessment was recorded at the time of ED arrival and discharge using a 10-cm visual analog scale. In addition, all patients received telephone follow-up at 5–7 days. This was performed by a blinded study investigator who utilized a standardized data collection instrument to assess the primary outcome of pain based on a 0–3 verbal rating scale (VRS: none = 0, mild = 1, moderate = 2, severe = 3) as well as functional status. In addition, all patients were assessed for possible side effects, medication compliance, and patient satisfaction (1–5 point scale, 1 = very unsatisfied, 5 = very satisfied).

We a priori arbitrarily chose a difference of 0.6 as a clinically important difference on the 0–3 pain scale. A preenrollment power calculation determined that 29 patients were needed in each group to have a power of 80% to detect a 0.6 average difference between the two groups, with a = 0.05 and SD of 0.8. Enrollment began in November 2005 and was completed in May 2009. Data were entered into Microsoft Excel for Windows (Microsoft Corporation, Redmond, WA) and transferred into SPSS for Windows (IBM, Armonk, NY) for statistical analysis. Categorical variables were analyzed by chisquared, interval data by Mann-Whitney, and continuous variables by Student’s t-test. All tests were two-tailed with alpha set at 0.05. The main study outcome was the subject’s pain at 5 days on the 0–3 scale. Secondary outcomes included a dichotomized pain scale (none or mild), whether the patient received further medical evaluation, whether the patient resumed normal household chores, whether the patient needed further evaluation from their personal doctor, whether the patient was able to return to work, and days out of work. Data analysis followed the intention-to-treat principle. The study was approved by the institutional review board. RESULTS Seventy-nine subjects were enrolled. Of these, 12 (15%) were lost to follow-up, leaving 32 and 35 patients, respectively, in the prednisone and placebo arms (Figure 1). The mean age was 40 (SD 9) years, and 30% (SD 6%) were female. The two study arms had similar demographics, initial and discharge ED pain scales, and pain prescriptions given at discharge, as seen in Table 1. The characteristics of subjects lost to follow-up differed little from those of the entire group (Table 1). The main study end point, pain at 5 days on the 0–3point scale, was similar between the two groups (absolute

Figure 1. Enrolled participants. F/U = follow-up.

Prednisone for Low Back Pain

3

Table 1. Baseline Characteristics Lost to Prednisone Placebo Follow-Up Number of subjects Age: mean (SD) Female (%) Race (%) Caucasian Hispanic Black Recall specific event causing the pain? (%) Hours since event (SD) Pain medication taken in last 24 h (%) NSAIDs Muscle relaxant Opioid Acetaminophen Tramadol History of back problems (%) Disc problem (%) History of back surgery (%) Laminectomy (%) Initial ED VAS (0–10) (SD) ED VAS at discharge (0–10) (SD) Prescriptions at discharge (%) Opioids Muscle relaxants NSAIDs

39 39 (8) 33

40 41 (9) 27

12 43 (6) 40

56 18 8 71

60 20 10 87

30 40 20 90

23 (15) 85

15 (15) 85

15 (4) 70

64 18 18 10 5 54 21 6 3 8.0 (1.4) 6.1 (2.3)

63 20 15 10 0 73 33 8 3 8.0 (1.5) 5.2 (2.1)

70 0 0 0 0 70 30 0 0 7.5 (1.2) 4.8 (2.6)

97 84 10

94 80 11

90 80 10

SD = standard deviation; NSAID = nonsteroidal antiinflammatory drug; ED = emergency department; VAS = visual analog scale.

difference 0.2, 95% confidence interval [CI] 0.2, 0.6), as seen in Table 2 and Figure 2. (Although the intent was to call patients after 5 days, the actual median length of time for the callbacks was 6 days for both groups, with the prednisone group having an interquartile range of 5 and 7 days and the placebo group, 5 and 6 days). As for secondary outcomes, more patients in the prednisone group than in the placebo group reported seeking addi-

tional medical treatment (40% vs. 18%, respectively, difference 22%; 95% CI 0, 43%) and there was a trend toward fewer days lost from work in the placebo group (difference 0.9 days, 95% CI 0.1, 1.8 days, p = 0.06). No differences were found in the other secondary outcomes of resuming normal activities or returning to work at follow-up call. During the follow-up telephone interview, the patients reported no significant side effects from the study or prescribed medications. Compliance with taking the study medication was similar in both groups. Of the 6 patients who did not finish taking the study medication (2 in the prednisone group and 4 in the placebo group), 3 gave the reason for this, namely being told to stop by a physician (2 patients) or family member (1 patient). DISCUSSION LBP is a common presenting problem in the ED. Friedman et al. estimate that there are at least 2.6 million ED visits per year for back pain in the US (6). Back pain represents a diverse group of disorders of the soft tissue, nerves, and bony structures. The ED treatment is largely supportive, with varying medications used to provide pain relief. One study of a national ED database, characterizing ED LBP patients, found that 62% received an opioid medication, 50% a nonsteroidal anti-inflammatory agent, 43% a muscle relaxant, and 11% a benzodiazepine (6). In this same study, 5% of US ED patients received corticosteroid therapy. Extrapolated among the 2.6 million yearly ED LBP patients, this represents approximately 127,000 patients annually. The theoretical basis for corticosteroid use in LBP is that pain involving spinal nerves is not only due to mechanical issues, but may be mediated by inflammatory changes (8). In addition, there is considerable evidence that favors local steroid injection of nerve roots for

Table 2. Outcome Measurements

Pain scale (0–3) at 5–7 days Dichotomized pain scale (none or mild) Required more pain medication at home? Was this medication prescribed in the ED? Did you take the study drug for 5 days? Did you seek further medical care for back pain? Have back pain now? Able to resume normal activities? Do you have a job? If so, return to work at time of follow-up call? Days of work lost (SD) Able to do normal house chores? Need more medication than have now? Satisfaction with ED treatment (1–5 scale)

Prednisone

Placebo

1.3 56% 65% 94% 94% 40% 84% 68% 88% 78% 2.1 63% 40% 4.9

1.1 69% 76% 88% 88% 18% 71% 68% 86% 80% 1.3 74% 38% 4.8

CI = confidence interval; ED = emergency department; SD = standard deviation.

Difference (95% CI) 0.2 ( 0.2, 0.6) 13% ( 36, 10%) 11% ( 33, 11%) 5% ( 13, 23%) 6% ( 8, 20%) 22% (0, 43%) 12% ( 6, 33%) 0% ( 23, 23%) 2% ( 15, 18%) 1% ( 22, 19%) 0.9 ( 0.1, 1.8) 11% ( 33, 11%) 2% ( 21, 26%) 0.0 ( 0.2, 0.3)

p Value 0.25 0.31 0.47 0.82 0.40 0.05 0.40 1.00 0.91 0.95 0.06 0.47 0.83 0.90

4

Figure 2. Number of patients with pain score (0–3) on followup (F/U). Pain score: 0 = none, 1 = mild, 2 = moderate, 3 = severe.

LBP (9–15). Multiple randomized controlled trials (RCTs) show improved pain relief, especially involving chronic radicular pain (10–14). The evidence for systemic corticosteroids (oral, intramuscular, or intravenous) is less robust. We found only seven RCTs in the literature (16–22). All but one involved parenteral corticosteroids; the one involving oral corticosteroids was a small study (27 patients total, recruited from both the ED and a primary care practice) and showed benefits in some measures of outcome (such as pain relief and disability scores), but no benefits in others (such as return to work) (21). The results of the seven RCTs have shown conflicting results, with several showing mild to moderate early pain relief and others showing no benefit (16–22). Of these seven RCTs, only two were entirely ED based. Both were reported by Friedman et al., were carried out in an urban ED setting, and involved the acute presentation of LBP treated with a single intramuscular methylprednisolone injection compared to placebo (20,22). The initial 2006 study involved musculoskeletal LBP and showed no benefit in any of the outcomes (20). The second study, published in 2008, only enrolled patients with LBP of radicular origin (22). This study showed a trend to decreased pain and significantly decreased disability at 1 month (22). The authors concluded that intramuscular corticosteroids may be useful for acute radicular LBP. Limitations Our study had several limitations. Although we attempted to enroll only musculoskeletal LBP patients (one of our inclusion criteria was LBP from a bending or twisting injury within the last 48 h), the clinical differentiation of musculoskeletal from radicular pain is imperfect. In addition, we allowed patients to be enrolled that had a history of back problems. Previous studies also used clinical parameters similar to ours. Some patients enrolled in the

B. Eskin et al.

study may have actually had pain that was not musculoskeletal LBP from a bending or twisting injury. Our inclusion and exclusion criteria did not absolutely exclude the possibility of other etiologies such as epidural abscess, infectious diskitis, epidural hematomas, and autoimmune disorders, but they do make them very unlikely. Although we did not specifically ask about side effects of taking steroids on the follow-up call, no patients reported adverse events. In any case, known side effects of steroids, such as hyperglycemia and gastrointestinal bleeding, would have been unlikely in our study because patients with diabetes or significant peptic ulcer disease were specifically excluded from the study to minimize the possibility of these side effects. Another limitation is that we measured the outcome at a single time point, 5–7 days. If there were a significant benefit from steroids earlier or later, we would not have seen that. On the other hand, most prior studies that show a benefit suggest that the effect of corticosteroids appears early and may decrease as follow-up duration is increased. The dose of corticosteroid utilized may represent another limitation; other studies have suggested benefit from higher-dose systemic corticosteroids (20). Of our 79 patients, 12 (15%) were lost to follow-up. A sensitivity analysis showed that if the patients in the prednisone group lost to follow-up had no pain on follow-up and the placebo group lost to follow-up had the same pain as those not lost to follow-up, our study would still have shown no difference between the groups. We used a different pain scale at follow-up than in the ED. All pain scales have advantages and disadvantages (23). Although we used the VAS scale in the ED, the primary outcome of our study was the level of pain at telephone follow-up. We felt that a VRS scale would be more easily and reliably understood by patients over the telephone than a VAS scale (24). At least 5 days had passed since the initial encounter and we did not mention the VAS scale during the telephone interview, so we doubt that patients would have confused the two pain scales during the follow-up call. We did not use a standardized protocol for analgesia given the patient in the ED and prescribed on discharge because this was felt to more accurately reflect actual clinical practice where the physician chooses medication based on factors such as the response of the patient to medication taken prior to coming to the ED and given the patient in the ED, the patient’s previous experience with pain medication, and the level of pain that the patient is in. Although this could have resulted in unequal analgesic treatment between the two groups, we felt it would be unlikely to occur because all investigators and participants were blinded to group allocation until after the study was completed. In fact, the pattern of prescriptions of pain medications after discharge from the ED was similar between the two groups (Table 1).

Prednisone for Low Back Pain

Our findings do not support the use of oral corticosteroid therapy in ED patients presenting with LBP to a community hospital. Further study may be needed to evaluate oral or parenteral corticosteroid efficacy in ED radicular LBP presentations. CONCLUSIONS We detected no benefit from oral corticosteroids in our population of ED patients with musculoskeletal LBP. Acknowledgments—The authors wish to thank Drs. Gene Lee and Christopher Peart for help with data collection. Barnet Eskin received financial support from Emergency Medical Associates Research Foundation.

REFERENCES 1. Deyo RA, Mirza SK, Martin BI. Back pain prevalence and visit rates: estimates from U.S. national surveys, 2002. Spine (Phila Pa 1976) 2006;31:2724–7. 2. Corwell BN. The emergency department evaluation, management, and treatment of back pain. Emerg Med Clin North Am 2010;28: 811–39. 3. Casazza BA. Diagnosis and treatment of acute low back pain. Am Fam Physician 2012;85:343–50. 4. Andersson GB. Epidemiological features of chronic low-back pain. Lancet 1999;354:581–5. 5. Wipf J, Deyo R. Low back pain. Med Clin North Am 1995;79: 231–46. 6. Friedman BW, Chilstrom M, Bijur PE, Gallagher EJ. Diagnostic testing and treatment of low back pain in United States emergency departments: a national perspective. Spine (Phila Pa 1976) 2010;35: E1406–11. 7. Friedman BW, O’Mahony S, Mulvey L, et al. One-week and 3month outcomes after an emergency department visit for undifferentiated musculoskeletal low back pain. Ann Emerg Med 2012; 59:128–33. 8. Burnett C, Day M. Recent advancements in the treatment of lumbar radicular pain. Curr Opin Anaesthesiol 2008;21:452–6.

5 9. Green LN. Dexamethasone in the management of symptoms due to herniated lumbar disc. J Neurol Neurosurg Psychiatry 1975;38: 1211–7. 10. Valat JP, Giraudeau B, Rozenberg S, et al. Epidural corticosteroid injections for sciatica: a randomized, double-blind, controlled clinical trial. Ann Rheum Dis 2003;62:639–43. 11. Arden NK, Price C, Reading I, et al., WEST Study Group. A multicentre randomized controlled trial of epidural corticosteroid injections for sciatica: the WEST study. Rheumatology 2005;44:1399–406. 12. Ng L, Chaudhary N, Sell P. The efficacy of corticosteroids in periradicular infiltration for chronic radicular pain. Spine (Phila Pa 1976) 2005;30:857–62. 13. Manchikanti L, Boswell MV, Singh V, et al. A randomized, controlled, double-blind trial of fluoroscopic caudal epidural Injections in the treatment of lumbar disc herniation and radiculitis. Spine (Phila Pa 1976) 2011;36:1897–905. 14. Kim D, Brown J. Efficacy and safety of lumbar epidural dexamethasone versus methylprednisolone in the treatment of lumbar radiculopathy: a comparison of soluble versus particulate steroids. Clin J Pain 2011;27:518–22. 15. Nampiaparampil DE, Nampiaparampil GM, Nampiaparampil RG. Oral opioid analgesics vs. spinal steroid injections for the treatment of low back pain syndromes. Am J Phys Med Rehabil 2012;91: 162–76. 16. Porsman O, Friis H. Prolapsed lumbar disc treated with intramuscularly administered dexamethasonephosphate: a prospectively planned, double-blind, controlled clinical trial in 52 patients. Scand J Rheumatol 1979;8:142–4. 17. Hedeboe J, Buhl M, Ramsing P. Effects of using dexamethasone and placebo in the treatment of prolapsed lumbar disc. Acta Neurol Scand 1982;65:6–10. 18. Haimovic I, Beresford H. Dexamethasone is not superior to placebo for treating lumbosacral radicular pain. Neurology 1986;36:1593–4. 19. Finckh A, Zufferey P, Scburch MA, et al. Short-term efficacy of intravenous pulse glucocorticoids in acute discogenic sciatica: a randomized controlled trial. Spine (Phila Pa 1976) 2006;31:377–81. 20. Friedman BW, Holden L, Esses D. Parenteral corticosteroids for emergency department patients with nonradicular low back pain. J Emerg Med 2006;31:365–70. 21. Holve RL, Barkan H. Oral steroids in initial treatment of acute sciatica. J Am Board Fam Med 2008;21:469–74. 22. Friedman BW, Esses D, Solorzano C, et al. A randomized placebocontrolled trial of single-dose IM corticosteroid for radicular low back pain. Spine (Phila Pa 1976) 2008;33:E624–9. 23. Todd KH. Pain assessment instruments for use in the emergency department. Emerg Med Clin North Am 2005;23:285–95. 24. Paice J, Cohen F. Validity of a verbally administered numeric rating scale to measure cancer pain intensity. Cancer Nurs 1997;20:88–93.

6

B. Eskin et al.

ARTICLE SUMMARY 1. Why is this topic important? Although corticosteroids are commonly used for musculoskeletal back pain, there is little evidence that patients, particularly those seen in emergency departments, benefit from their use. 2. What does this study attempt to show? We attempted to determine if a five day course of prednisone benefits emergency department patients with musculoskeletal back pain. 3. What are the key findings? A five day course of prednisone compared to placebo does not reduce back pain at the end of treatment and may actually cause harm: more patients in the prednisone than placebo group sought additional treatment after emergency department discharge and there was a trend to losing more days from work as well. 4. How is patient care impacted? Oral corticosteroids should not be prescribed for patients with musculoskeletal back pain.

Prednisone for emergency department low back pain: a randomized controlled trial.

Although oral corticosteroids are commonly given to emergency department (ED) patients with musculoskeletal low back pain (LBP), there is little evide...
277KB Sizes 0 Downloads 4 Views