The Journal of Emergency Medicine, Vol. -, No. -, pp. 1–6, 2013 Published by Elsevier Inc. Printed in the USA 0736-4679/$ - see front matter
http://dx.doi.org/10.1016/j.jemermed.2012.12.014
Brief Reports INTRAVENOUS LIDOCAINE FOR THE EMERGENCY DEPARTMENT TREATMENT OF ACUTE RADICULAR LOW BACK PAIN, A RANDOMIZED CONTROLLED TRIAL David A. Tanen, MD,* Mai Shimada, MD,† D. Chris Danish, DO,* Frank Dos Santos, DO,‡ Martin Makela, MD,§ and Robert H. Riffenburgh, PHDjj *Department of Emergency Medicine, Naval Medical Center San Diego, San Diego, California, †University of Tokyo Medical School, Tokyo, Japan, ‡Department of Emergency Medicine, Naval Medical Center Portsmouth, Portsmouth, Virginia, §Division of Emergency Medicine, University of Washington, Seattle, Washington, and jjClinical Investigations Department, Naval Medical Center San Diego, San Diego, California Corresponding Address: David A. Tanen, MD, Department of Emergency Medicine, Harbor-UCLA Medical Center, 1000 West Carson, Torrance, CA 90509
interval [CI] 74–98 vs. 79; 95% CI 64–94; p = 0.278). Median VAS scores from baseline to 60 min significantly declined in both groups (lidocaine [8; 95% CI 0–23; p = 0.003]; ketorolac [14; 95% CI 0–28; p = 0.007]), with no significant difference in the degree of reduction between groups (p = 0.835). Rescue medication was required by 67% receiving lidocaine, compared to 50% receiving ketorolac. No significant change in PRS between groups was found at the conclusion or at the follow-up. Conclusion: Intravenous lidocaine failed to clinically alleviate the pain associated with acute radicular low back pain. Published by Elsevier Inc.
, Abstract—Background: Acute radicular back pain is a frequent complaint of patients presenting to the Emergency Department. Study Objective: Determine the efficacy of intravenous lidocaine when compared to ketorolac for the treatment of acute radicular low back pain. Methods: Randomized double-blind study of 41 patients aged 18–55 years presenting with acute radicular low back pain. Patients were randomized to receive either 100 mg lidocaine or 30 mg ketorolac intravenously over 2 min. A 100-mm visual analog scale (VAS) was used to assess pain at Time 0 (baseline), and 20, 40, and 60 minutes. Changes in [median] VAS scores were compared over time (within groups) by the signed-rank test and between groups by the rank-sum test. A 5-point Pain Relief Scale (PRS) was administered at the conclusion of the study (60 min) and again at 1 week by telephone follow-up; [median] scores were compared between groups by rank-sum. Results: Forty-four patients were recruited; 41 completed the study (21 lidocaine, 20 ketorolac). Initial VAS scores were not significantly different between the lidocaine and ketorolac groups (83; 95% confidence
, Keywords—lidocaine; ketorolac; radicular; pain
INTRODUCTION Acute radicular back pain is a frequent complaint in the Emergency Department (ED) and is usually caused by nerve impingement or inflammation (1–3). It often presents as a shooting, electric pain that radiates into the buttocks or posterior thigh of patients and is described as an excruciating, lancinating pain that is often recalcitrant to available over-the-counter medications. The course of this neurogenic pain is persistent, with many relapses often affecting the patient’s ability to play sports, work, or even ambulate (1–4).
Presented at the American College of Emergency Physicians Scientific Assembly Research Forum, October 2011, San Francisco, CA. The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the U.S. Navy, Department of Defense, or the U.S. government. Reprints are not available.
RECEIVED: 1 February 2012; FINAL SUBMISSION RECEIVED: 6 October 2012; ACCEPTED: 4 December 2012 1
2
D. A. Tanen et al.
Multiple medications have been explored for the treatment of acute neuropathic low back pain, but few have made a clinically significant impact (5). Intravenous lidocaine in dose ranges from 1.5 to 5.0 mg/kg has been advocated for the reduction of various neurologic pain syndromes (6–12). Additionally, intravenous lidocaine has been reported to reduce the level of the neuropathic pain for 3–21 days after infusion (13). Our objective was to determine the efficacy of a one-time bolus administration of intravenous lidocaine on reducing the reported intensity of radicular back pain in patients presenting to the ED. We chose to conduct a randomized clinical trial comparing intravenous lidocaine to intravenous ketorolac, a well-known and commonly prescribed non-steroidal anti-inflammatory medication. METHODS Study Design This was a randomized controlled double-blinded study to evaluate the efficacy of intravenous lidocaine when compared to ketorolac for the ED treatment of acute radicular back pain. The medical center’s institutional review board for protection of human subjects approved the study. Written informed consent was obtained from all participants and an investigational new drug application was filed with the United States Food and Drug Administration. Study Setting and Population The study was conducted in the ED of a tertiary care medical center that serves beneficiaries of active duty and retired military personnel and has an annual census of 65,000. A convenience sample of patients aged 15–55 years who presented with the complaint of radicular low back pain were eligible. Patients were recruited any time of the day based on the rotating scheduling of our research assistants. Study Protocol Patients were eligible for enrollment if they met criteria for radicular back pain that were defined as the acute onset of back pain that possessed a radicular component as determined by the treating physician. Patients were excluded if they were pregnant, had a fever $38.1 C (100.5 F), diastolic blood pressure of $105 mm Hg, or met any of the following criteria: medical history of peptic ulcer disease, renal insufficiency, structural or ischemic cardiac disease, or persistent neurological deficits. Patients with a history of allergic reactions to amide local anesthetics were also excluded, along with patients with
an initial pain score of 25 mm or less on the 100-mm non-hatched visual analog scale (VAS). After obtaining informed consent and a negative urine pregnancy test result for female patients, patients were asked by a research assistant to grade their baseline pain. After the baseline data were obtained, an intravenous line was placed and patients were prospectively randomized to receive intravenously either 100 mg lidocaine or 30 mg ketorolac over 2 min, followed by a 10-cc normal saline flush. Randomization was accomplished by the use of a computerized random numbers table. The study medication was coded and was drawn up in similarappearing syringes and administered by a nurse who was not party to the study. Both the investigator and the patient remained blinded to the medication delivered until the code was broken at the close of enrollment. After the infusion of the study medication, patients were asked to grade their pain on the VAS at 20-min intervals until Time 60 min without viewing previous scores. Neurologic adverse events were recorded by actively questioning all subjects about tingling, numbness, or drowsiness starting at 5 min after the medication infusion and continuing at 20-min intervals. Heart rate, respiratory rate, and pulse oximetry were continually monitored, and blood pressure was recorded every 5 min. Patients also underwent continuous three-lead electrocardiographic monitoring throughout the study. The study concluded at Time 60 min. If the subject’s radicular back pain was not sufficiently relieved by the study medication as reported by the patient, rescue therapy was instituted at the discretion of the treating physician, with the exception of the use of both study medications. The patient’s pain relief was also assessed at the conclusion of the study and 1 week after the conclusion using a Pain Relief Scale (PRS): 0 = worse pain, 1 = no change in pain, 2 = slight pain relief, 3 = moderate pain relief, 4 = a lot of pain relief, 5 = complete pain relief. Data Analysis Median VAS scores for pain were calculated and differences in VAS scores from Time 0 (baseline) to Time 60 min (conclusion of study) were compared across groups using Wilcoxon’s signed-rank test and between groups using a rank-sum test. Data from the PRS were analyzed similarly. A Fisher’s exact test of contingency compared numbers of patients rescued vs. not rescued against drug type. Stata 12.0 software (Stata Corp, College Station TX) was used for data analysis. Sample Size Determination Power analyses were based on t-tests of VAS differences because the data irregularity seen after data acquisition
Lidocaine for Back Pain
3
Randomized patients n = 44
i.v. Lidocaine n = 22
Patient Withdrawal n=1
Completed Study n = 21
i.v. Ketorolac n = 22
Patient Withdrawal or Invalid Data n=2
Completed Study n = 20
Figure 1. Consort diagram of patients enrolled into the study. i.v. = intravenous.
was not anticipated. The commonly chosen clinically significant difference of 13 mm was used as a detection interval. An SD was not found in the medical literature. The closest information was two VAS range values of 60 mm found in Finnerup et al. (12). An assumption that the 12 patients’ data spanned 95% of the possible data range would imply an SD of approximately onefourth the range, or 15. A power analysis based on a = 0.05 and power = 0.80 yielded the requirement for 21 patients per group. We chose to enroll 22, for a total of 44 patients, providing a power of 0.82 in a between-group test and of 0.98 in a within-group (change over 60 min) test. We completed the study with 20 ketorolac and 21 lidocaine patients, providing powers of 0.79 between groups, 0.97 over time within ketorolac, and 0.98 within lidocaine. The use of rank tests would reduce these powers slightly, to a vicinity of 0.74 between and 0.96 within. RESULTS Forty-four patients were recruited and 41 met inclusion criteria and completed the study (21 in the lidocaine group and 20 in the ketorolac group). One patient in the ketorolac and one patient in the lidocaine group withdrew at the 20-min time point due to a lack of improvement in symptoms (initial VAS scores: 100 and 82, respectively). One patient in the ketorolac group was also excluded because the initial pain VAS scale was reported as 8 mm (Figure 1). Baseline data, including pain, age, gender, and weight, are represented in Table 1. Initial median VAS scores for pain were not significantly different between lidocaine and ketorolac groups (83; 95% confidence interval [CI] 74–98 vs. 79; 95% CI 64–94; p = 0.278). Median VAS scores from baseline to 60 min were significantly reduced within each group (lidocaine [8; 95% CI 0–23; p = 0.003] and ketorolac [14; 95% CI 0–28; p = 0.007]), but no difference was found between the degree of reduction between groups (p = 0.835). Graphi-
cal representation of each patient over time is shown in Figure 2, and group median VAS over time is illustrated in Figure 3. Although not statistically significant (p = 0.350), patients in the intravenous lidocaine group required rescue medication 67% of the time, as compared to 50% in the intravenous ketorolac group. There was also no difference detected in the Patient Relief Scores that were obtained at the conclusion of the study (medians 2, 2; p = 0.314) or at the 1-week follow-up (median differences 0, 0; p = 0.388). DISCUSSION Currently, there is no criterion standard for the abortive treatment of acute radicular back pain in the ED, although it is typically treated with a combination of non-steroidal anti-inflammatory drugs (NSAIDs) and opioids (5,14). Because opioids can prolong the length of stay, may induce histamine release causing allergic-like reactions or hypotension, and may lead to dependence, NSAIDs are often prescribed as the first-line treatment, but are often minimally effective (2,4,14). At this time, the search continues for an optimal therapy that would work quickly and have minimal side effects so that patients can obtain relief from their symptoms and be able to be discharged from the ED in an expedited fashion (2,4,5).
Table 1. Patient Demographic Characteristics and Initial Pain Scores for Each Study Group Baseline Data (Mean 6 SD or Count) Characteristic
Lidocaine
Ketorolac
Age (years) Sex (number) Female Male Weight (kg) Pain, mm
36 6 10
39 6 12
11 11 195 6 36 84 6 15
8 14 195 6 38 78 6 18
4
D. A. Tanen et al.
Figure 2. Individual pain visual analog scale scores over time for the ketorolac and lidocaine groups. VAS = visual analog scale.
The mechanism of action of the two study treatments differs markedly. Ketorolac, an NSAID, exerts its effect by inhibiting the enzyme cyclooxygenase, resulting in the decreased production of prostaglandins, which in turn are responsible for sensitizing spinal neurons to pain (15). Lidocaine, like most local anesthetics, works by blocking voltage-gated sodium channels in neuronal cell membranes, thereby decreasing depolarization and pain signal propagation (16,17). In our small study, although intravenous lidocaine was found to be statistically effective in reducing radicular pain, it did not reach the threshold of a 13-mm reduction on the VAS that has been previously reported as being the minimum difference needed to reach clinical significance (18). This finding was further supported by the fact that 67% of the patients receiving the intravenous lidocaine required rescue therapy. We also did not find that
Lidocaine
0
20
40
60
80
100
Ketorolac
Pre
20 min
40 min 60 min
Pre
20 min 40 min 60 min
Figure 3. Box-and-Whisker diagram representing the quartiles and outliers for the median group visual analog scale scores over time for the ketorolac and lidocaine groups.
intravenous lidocaine had any pronounced effect on residual pain when the patients were followed-up 1 week after they were discharged from the ED. In comparison, similar to previous studies on NSAIDs, we found ketorolac to be minimally clinically effective in reducing radicular back pain (2,4,14). Although intravenous lidocaine did not seem to be clinically useful for treatment of acute radicular back pain in our study, it was interesting to note that there was at least one patient who responded to the therapy, with pain scores decreasing from 100 mm to 0 mm on the VAS. It may be that in a larger study, a subgroup of patients responsive to intravenous lidocaine may be identified. In addition, because we employed a relatively low dose of intravenous lidocaine, future studies should concentrate their efforts on higher dosing regimens that would need to be given over a prolonged period of time to reduce potential toxicity. Limitations The major limitation of the study is in the diagnosis of acute radicular back pain. Although we used a standard definition, we might have included patients with musculoskeletal complaints who did not have a neurogenic etiology for their back pain. Additionally, we did not screen for repeat ED users or chronicity of the radicular back pain before enrolling patients in the study. The study was designed to enroll patients with acute episodes of radicular back pain that could represent a new occurrence or the exacerbation of a chronic one. Randomization should have decreased the likelihood that one of the treatment group arms received a disproportionate share of the non-radicular patients and chronic pain patients; however, we cannot say that a larger trial would identify a subgroup of patients with acute radicular back pain who
Lidocaine for Back Pain
would benefit from intravenous lidocaine. The lack of response to lidocaine might also have been the result of a dosing effect. We utilized the non-weight-based dose of 100 mg lidocaine that averaged out to just over 1.1 mg/kg in our patient population. Potentially, higher doses may have yielded a better outcome. Because we chose to study a bolus treatment option for the lidocaine, we were limited by the potential acute toxicity that could be associated with higher doses when the drug is given over 2 min. CONCLUSION Intravenous lidocaine failed to clinically alleviate the pain associated with acute radicular low back pain. Acknowledgment—This study was supported by a grant from the Clinical Investigations Department at the Naval Medical Center San Diego.
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. Deyo RA, Weinstein JN. Low back pain. N Engl J Med 2001;344: 363–70. 3. Waterman BR, Belmont PJ Jr, Schoenfeld AJ. Low back pain in the United States: incidence and risk factors for presentation in the emergency setting. Spine J 2012;12:63–70. 4. Pengel LH, Herbert RD, Maher CG, Refshauge KM. Acute low back pain: a systematic review of its prognosis. BMJ 2003;327:323.
5 5. van Tulder MW, Scholten RJPM, Koes BW, Deyo RA. Non steroidal anti-inflammatory drugs for low back pain. Cochrane Database Syst Rev 2000;2:CD000396. 6. Ferrante MF, Paggioli J, Cherukuri S, Arthur GR. The analgesic response to intravenous lidocaine in the treatment of neuropathic pain. Anesth Analg 1995;82:91–7. 7. Medrik-Goldberg T, Lifschitz D, Pud D, et al. Intravenous lidocaine, amantadine, and placebo in the treatment of sciatica; a double-blind, randomized, controlled study. Reg Anesth Pain Med 1999;24:534–40. 8. Kvarnstrom A, Karlsten R, Quiding H, et al. The effectiveness of intravenous ketamine and lidocaine on peripheral neuropathic pain. Acta Anaesthesiol Scand 2003;47:868–77. 9. Soleimanpour H, Hassanzadeh K, Mohammadi DA, et al. Parenteral lidocaine for treatment of intractable renal colic: a case series. J Med Case Rep 2011;5:256–60. 10. Attal N, Gaude V, Brasseur L, et al. Intravenous lidocaine in central pain: a double-blind, placebo-controlled, psychophysical study. Neurology 2000;54:564–74. 11. Fujii J, Fukushima T, Ishii M, et al. The efficacy of intravenous lidocaine for acute herpetic pain – placebo controlled trial. Masui 2009;58:1413–7. 12. Finnerup NB, Biering-Sorensen F, Johannesen IL, et al. Intravenous lidocaine relieves spinal cord injury pain: a randomized controlled study. Anesthesiology 2005;102:1023–30. 13. Bach FW, Jensen TS, Kastrup J, et al. The effect of intravenous lidocaine on nociceptive processing in diabetic neuropathy. Pain 1990;40:29–34. 14. Veenema KR, Leahey N, Schneider S. Ketorolac versus meperidine: ED treatment of severe musculoskeletal low back pain. Am J Emerg Med 2000;18:404–7. 15. Catapano MS. The analgesic efficacy of ketorolac for acute pain. J Emerg Med 1996;14:67–75. 16. Tanelian DL, MacIver MD. Analgesic concentrations of lidocaine suppress tonic A-delta and C fiber discharges produced by acute injury. Anesthesiology 1991;74:934–6. 17. Chabal C, Russell LC, Burchiel KJ. The effect of intravenous lidocaine, tocainide, and mexiletine on spontaneously active fibers originating in rat sciatic neuromas. Pain 1989;38:333–8. 18. Todd KH, Funk KG, Funk JF, Bonacci R. Clinical significance of reported changes in pain severity. Ann Emerg Med 1996;27:485–9.
6
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ARTICLE SUMMARY 1. Why is this topic important? Radicular low back pain is a common presentation to the Emergency Department. Currently there are no consistently effective strategies for relieving radicular low back pain. 2. What does this study attempt to show? Determine the efficacy of intravenous lidocaine in the treatment of acute radicular low back pain. 3. What are the key findings? A 100-mg bolus of intravenous lidocaine was not clinically useful for treatment of acute radicular back pain. 4. How is patient care impacted? The search for effective therapy for the treatment of acute radicular back pain continues and further studies into higher-dose lidocaine infusions are underway.
http://dx.doi.org/10.1016/j.jemermed.2012.12.014
Brief Reports INTRAVENOUS LIDOCAINE FOR THE EMERGENCY DEPARTMENT TREATMENT OF ACUTE RADICULAR LOW BACK PAIN, A RANDOMIZED CONTROLLED TRIAL David A. Tanen, MD,* Mai Shimada, MD,† D. Chris Danish, DO,* Frank Dos Santos, DO,‡ Martin Makela, MD,§ and Robert H. Riffenburgh, PHDjj *Department of Emergency Medicine, Naval Medical Center San Diego, San Diego, California, †University of Tokyo Medical School, Tokyo, Japan, ‡Department of Emergency Medicine, Naval Medical Center Portsmouth, Portsmouth, Virginia, §Division of Emergency Medicine, University of Washington, Seattle, Washington, and jjClinical Investigations Department, Naval Medical Center San Diego, San Diego, California Corresponding Address: David A. Tanen, MD, Department of Emergency Medicine, Harbor-UCLA Medical Center, 1000 West Carson, Torrance, CA 90509
interval [CI] 74–98 vs. 79; 95% CI 64–94; p = 0.278). Median VAS scores from baseline to 60 min significantly declined in both groups (lidocaine [8; 95% CI 0–23; p = 0.003]; ketorolac [14; 95% CI 0–28; p = 0.007]), with no significant difference in the degree of reduction between groups (p = 0.835). Rescue medication was required by 67% receiving lidocaine, compared to 50% receiving ketorolac. No significant change in PRS between groups was found at the conclusion or at the follow-up. Conclusion: Intravenous lidocaine failed to clinically alleviate the pain associated with acute radicular low back pain. Published by Elsevier Inc.
, Abstract—Background: Acute radicular back pain is a frequent complaint of patients presenting to the Emergency Department. Study Objective: Determine the efficacy of intravenous lidocaine when compared to ketorolac for the treatment of acute radicular low back pain. Methods: Randomized double-blind study of 41 patients aged 18–55 years presenting with acute radicular low back pain. Patients were randomized to receive either 100 mg lidocaine or 30 mg ketorolac intravenously over 2 min. A 100-mm visual analog scale (VAS) was used to assess pain at Time 0 (baseline), and 20, 40, and 60 minutes. Changes in [median] VAS scores were compared over time (within groups) by the signed-rank test and between groups by the rank-sum test. A 5-point Pain Relief Scale (PRS) was administered at the conclusion of the study (60 min) and again at 1 week by telephone follow-up; [median] scores were compared between groups by rank-sum. Results: Forty-four patients were recruited; 41 completed the study (21 lidocaine, 20 ketorolac). Initial VAS scores were not significantly different between the lidocaine and ketorolac groups (83; 95% confidence
, Keywords—lidocaine; ketorolac; radicular; pain
INTRODUCTION Acute radicular back pain is a frequent complaint in the Emergency Department (ED) and is usually caused by nerve impingement or inflammation (1–3). It often presents as a shooting, electric pain that radiates into the buttocks or posterior thigh of patients and is described as an excruciating, lancinating pain that is often recalcitrant to available over-the-counter medications. The course of this neurogenic pain is persistent, with many relapses often affecting the patient’s ability to play sports, work, or even ambulate (1–4).
Presented at the American College of Emergency Physicians Scientific Assembly Research Forum, October 2011, San Francisco, CA. The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the U.S. Navy, Department of Defense, or the U.S. government. Reprints are not available.
RECEIVED: 1 February 2012; FINAL SUBMISSION RECEIVED: 6 October 2012; ACCEPTED: 4 December 2012 1
2
D. A. Tanen et al.
Multiple medications have been explored for the treatment of acute neuropathic low back pain, but few have made a clinically significant impact (5). Intravenous lidocaine in dose ranges from 1.5 to 5.0 mg/kg has been advocated for the reduction of various neurologic pain syndromes (6–12). Additionally, intravenous lidocaine has been reported to reduce the level of the neuropathic pain for 3–21 days after infusion (13). Our objective was to determine the efficacy of a one-time bolus administration of intravenous lidocaine on reducing the reported intensity of radicular back pain in patients presenting to the ED. We chose to conduct a randomized clinical trial comparing intravenous lidocaine to intravenous ketorolac, a well-known and commonly prescribed non-steroidal anti-inflammatory medication. METHODS Study Design This was a randomized controlled double-blinded study to evaluate the efficacy of intravenous lidocaine when compared to ketorolac for the ED treatment of acute radicular back pain. The medical center’s institutional review board for protection of human subjects approved the study. Written informed consent was obtained from all participants and an investigational new drug application was filed with the United States Food and Drug Administration. Study Setting and Population The study was conducted in the ED of a tertiary care medical center that serves beneficiaries of active duty and retired military personnel and has an annual census of 65,000. A convenience sample of patients aged 15–55 years who presented with the complaint of radicular low back pain were eligible. Patients were recruited any time of the day based on the rotating scheduling of our research assistants. Study Protocol Patients were eligible for enrollment if they met criteria for radicular back pain that were defined as the acute onset of back pain that possessed a radicular component as determined by the treating physician. Patients were excluded if they were pregnant, had a fever $38.1 C (100.5 F), diastolic blood pressure of $105 mm Hg, or met any of the following criteria: medical history of peptic ulcer disease, renal insufficiency, structural or ischemic cardiac disease, or persistent neurological deficits. Patients with a history of allergic reactions to amide local anesthetics were also excluded, along with patients with
an initial pain score of 25 mm or less on the 100-mm non-hatched visual analog scale (VAS). After obtaining informed consent and a negative urine pregnancy test result for female patients, patients were asked by a research assistant to grade their baseline pain. After the baseline data were obtained, an intravenous line was placed and patients were prospectively randomized to receive intravenously either 100 mg lidocaine or 30 mg ketorolac over 2 min, followed by a 10-cc normal saline flush. Randomization was accomplished by the use of a computerized random numbers table. The study medication was coded and was drawn up in similarappearing syringes and administered by a nurse who was not party to the study. Both the investigator and the patient remained blinded to the medication delivered until the code was broken at the close of enrollment. After the infusion of the study medication, patients were asked to grade their pain on the VAS at 20-min intervals until Time 60 min without viewing previous scores. Neurologic adverse events were recorded by actively questioning all subjects about tingling, numbness, or drowsiness starting at 5 min after the medication infusion and continuing at 20-min intervals. Heart rate, respiratory rate, and pulse oximetry were continually monitored, and blood pressure was recorded every 5 min. Patients also underwent continuous three-lead electrocardiographic monitoring throughout the study. The study concluded at Time 60 min. If the subject’s radicular back pain was not sufficiently relieved by the study medication as reported by the patient, rescue therapy was instituted at the discretion of the treating physician, with the exception of the use of both study medications. The patient’s pain relief was also assessed at the conclusion of the study and 1 week after the conclusion using a Pain Relief Scale (PRS): 0 = worse pain, 1 = no change in pain, 2 = slight pain relief, 3 = moderate pain relief, 4 = a lot of pain relief, 5 = complete pain relief. Data Analysis Median VAS scores for pain were calculated and differences in VAS scores from Time 0 (baseline) to Time 60 min (conclusion of study) were compared across groups using Wilcoxon’s signed-rank test and between groups using a rank-sum test. Data from the PRS were analyzed similarly. A Fisher’s exact test of contingency compared numbers of patients rescued vs. not rescued against drug type. Stata 12.0 software (Stata Corp, College Station TX) was used for data analysis. Sample Size Determination Power analyses were based on t-tests of VAS differences because the data irregularity seen after data acquisition
Lidocaine for Back Pain
3
Randomized patients n = 44
i.v. Lidocaine n = 22
Patient Withdrawal n=1
Completed Study n = 21
i.v. Ketorolac n = 22
Patient Withdrawal or Invalid Data n=2
Completed Study n = 20
Figure 1. Consort diagram of patients enrolled into the study. i.v. = intravenous.
was not anticipated. The commonly chosen clinically significant difference of 13 mm was used as a detection interval. An SD was not found in the medical literature. The closest information was two VAS range values of 60 mm found in Finnerup et al. (12). An assumption that the 12 patients’ data spanned 95% of the possible data range would imply an SD of approximately onefourth the range, or 15. A power analysis based on a = 0.05 and power = 0.80 yielded the requirement for 21 patients per group. We chose to enroll 22, for a total of 44 patients, providing a power of 0.82 in a between-group test and of 0.98 in a within-group (change over 60 min) test. We completed the study with 20 ketorolac and 21 lidocaine patients, providing powers of 0.79 between groups, 0.97 over time within ketorolac, and 0.98 within lidocaine. The use of rank tests would reduce these powers slightly, to a vicinity of 0.74 between and 0.96 within. RESULTS Forty-four patients were recruited and 41 met inclusion criteria and completed the study (21 in the lidocaine group and 20 in the ketorolac group). One patient in the ketorolac and one patient in the lidocaine group withdrew at the 20-min time point due to a lack of improvement in symptoms (initial VAS scores: 100 and 82, respectively). One patient in the ketorolac group was also excluded because the initial pain VAS scale was reported as 8 mm (Figure 1). Baseline data, including pain, age, gender, and weight, are represented in Table 1. Initial median VAS scores for pain were not significantly different between lidocaine and ketorolac groups (83; 95% confidence interval [CI] 74–98 vs. 79; 95% CI 64–94; p = 0.278). Median VAS scores from baseline to 60 min were significantly reduced within each group (lidocaine [8; 95% CI 0–23; p = 0.003] and ketorolac [14; 95% CI 0–28; p = 0.007]), but no difference was found between the degree of reduction between groups (p = 0.835). Graphi-
cal representation of each patient over time is shown in Figure 2, and group median VAS over time is illustrated in Figure 3. Although not statistically significant (p = 0.350), patients in the intravenous lidocaine group required rescue medication 67% of the time, as compared to 50% in the intravenous ketorolac group. There was also no difference detected in the Patient Relief Scores that were obtained at the conclusion of the study (medians 2, 2; p = 0.314) or at the 1-week follow-up (median differences 0, 0; p = 0.388). DISCUSSION Currently, there is no criterion standard for the abortive treatment of acute radicular back pain in the ED, although it is typically treated with a combination of non-steroidal anti-inflammatory drugs (NSAIDs) and opioids (5,14). Because opioids can prolong the length of stay, may induce histamine release causing allergic-like reactions or hypotension, and may lead to dependence, NSAIDs are often prescribed as the first-line treatment, but are often minimally effective (2,4,14). At this time, the search continues for an optimal therapy that would work quickly and have minimal side effects so that patients can obtain relief from their symptoms and be able to be discharged from the ED in an expedited fashion (2,4,5).
Table 1. Patient Demographic Characteristics and Initial Pain Scores for Each Study Group Baseline Data (Mean 6 SD or Count) Characteristic
Lidocaine
Ketorolac
Age (years) Sex (number) Female Male Weight (kg) Pain, mm
36 6 10
39 6 12
11 11 195 6 36 84 6 15
8 14 195 6 38 78 6 18
4
D. A. Tanen et al.
Figure 2. Individual pain visual analog scale scores over time for the ketorolac and lidocaine groups. VAS = visual analog scale.
The mechanism of action of the two study treatments differs markedly. Ketorolac, an NSAID, exerts its effect by inhibiting the enzyme cyclooxygenase, resulting in the decreased production of prostaglandins, which in turn are responsible for sensitizing spinal neurons to pain (15). Lidocaine, like most local anesthetics, works by blocking voltage-gated sodium channels in neuronal cell membranes, thereby decreasing depolarization and pain signal propagation (16,17). In our small study, although intravenous lidocaine was found to be statistically effective in reducing radicular pain, it did not reach the threshold of a 13-mm reduction on the VAS that has been previously reported as being the minimum difference needed to reach clinical significance (18). This finding was further supported by the fact that 67% of the patients receiving the intravenous lidocaine required rescue therapy. We also did not find that
Lidocaine
0
20
40
60
80
100
Ketorolac
Pre
20 min
40 min 60 min
Pre
20 min 40 min 60 min
Figure 3. Box-and-Whisker diagram representing the quartiles and outliers for the median group visual analog scale scores over time for the ketorolac and lidocaine groups.
intravenous lidocaine had any pronounced effect on residual pain when the patients were followed-up 1 week after they were discharged from the ED. In comparison, similar to previous studies on NSAIDs, we found ketorolac to be minimally clinically effective in reducing radicular back pain (2,4,14). Although intravenous lidocaine did not seem to be clinically useful for treatment of acute radicular back pain in our study, it was interesting to note that there was at least one patient who responded to the therapy, with pain scores decreasing from 100 mm to 0 mm on the VAS. It may be that in a larger study, a subgroup of patients responsive to intravenous lidocaine may be identified. In addition, because we employed a relatively low dose of intravenous lidocaine, future studies should concentrate their efforts on higher dosing regimens that would need to be given over a prolonged period of time to reduce potential toxicity. Limitations The major limitation of the study is in the diagnosis of acute radicular back pain. Although we used a standard definition, we might have included patients with musculoskeletal complaints who did not have a neurogenic etiology for their back pain. Additionally, we did not screen for repeat ED users or chronicity of the radicular back pain before enrolling patients in the study. The study was designed to enroll patients with acute episodes of radicular back pain that could represent a new occurrence or the exacerbation of a chronic one. Randomization should have decreased the likelihood that one of the treatment group arms received a disproportionate share of the non-radicular patients and chronic pain patients; however, we cannot say that a larger trial would identify a subgroup of patients with acute radicular back pain who
Lidocaine for Back Pain
would benefit from intravenous lidocaine. The lack of response to lidocaine might also have been the result of a dosing effect. We utilized the non-weight-based dose of 100 mg lidocaine that averaged out to just over 1.1 mg/kg in our patient population. Potentially, higher doses may have yielded a better outcome. Because we chose to study a bolus treatment option for the lidocaine, we were limited by the potential acute toxicity that could be associated with higher doses when the drug is given over 2 min. CONCLUSION Intravenous lidocaine failed to clinically alleviate the pain associated with acute radicular low back pain. Acknowledgment—This study was supported by a grant from the Clinical Investigations Department at the Naval Medical Center San Diego.
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ARTICLE SUMMARY 1. Why is this topic important? Radicular low back pain is a common presentation to the Emergency Department. Currently there are no consistently effective strategies for relieving radicular low back pain. 2. What does this study attempt to show? Determine the efficacy of intravenous lidocaine in the treatment of acute radicular low back pain. 3. What are the key findings? A 100-mg bolus of intravenous lidocaine was not clinically useful for treatment of acute radicular back pain. 4. How is patient care impacted? The search for effective therapy for the treatment of acute radicular back pain continues and further studies into higher-dose lidocaine infusions are underway.
