A Randomized Trial Comparing the Efficacy of Five Oral Analgesics for Treatment of Acute Musculoskeletal Extremity Pain in the Emergency Department.

STUDY OBJECTIVE: We compare the efficacy and adverse effects of 5 oral analgesics in emergency department (ED) patients aged 21 to 64 years with acute musculoskeletal pain. METHODS: This was a randomized clinical trial conducted in 2 urban EDs. Patients received 400 mg ibuprofen/1,000 mg acetaminophen, 800 mg ibuprofen/1,000 mg acetaminophen, 30 mg codeine/300 mg acetaminophen, 5 mg hydrocodone/300 mg acetaminophen, or 5 mg oxycodone/325 mg acetaminophen. The primary outcome was change in pain before administration of medication (baseline) to 1 hour postbaseline. A numeric rating scale was used, varying from 0="no pain" to 10="worst imaginable pain." Secondary outcomes included receipt of rescue medication and adverse effects at 1 and 2 hours postbaseline. ANOVA was used to test differences in the primary outcome between treatment groups. RESULTS: Six hundred participants, predominantly men and Latino, were enrolled. Change in pain from baseline to 60 minutes did not differ by treatment (P=.69). The mean change in pain in numeric rating scale units was 400 mg ibuprofen/1,000 mg acetaminophen 3.0 (95% confidence interval [CI] 2.6 to 3.5); 800 mg ibuprofen/1,000 mg acetaminophen 3.0 (95% CI 2.5 to 3.5), 30 mg codeine/300 mg acetaminophen 3.4 (95% CI 2.9 to 3.9), 5 mg hydrocodone/300 mg acetaminophen 3.1 (95% CI 2.7 to 3.5), and 5 mg oxycodone/325 mg acetaminophen 3.3 (95% CI 2.8 to 3.7). Rescue medication was received before 1 hour had elapsed by 2 patients receiving 400 mg ibuprofen/1,000 mg acetaminophen (1.7%), 3 patients receiving 800 mg ibuprofen/1,000 mg acetaminophen (2.5%), zero patients receiving 30 mg codeine/300 mg acetaminophen (0.0%), 3 patients receiving 5 mg hydrocodone/300 mg acetaminophen (2.5%), and zero patients receiving 5 mg oxycodone/325 mg acetaminophen (0.0%) (P=.21). More patients who received opioids were nauseated or vomited compared with those who did not: 6.7% versus 1.7% (5.0% difference; 95% CI 1.7% to 8.2%). The findings at 2 hours were similar. CONCLUSION: No analgesic was more efficacious than others 1 or 2 hours after baseline. There was significantly more nausea and vomiting among patients treated with opioids.

A Randomized, Double-Dummy, Emergency Department-Based Study of Greater Occipital Nerve Block With Bupivacaine vs Intravenous Metoclopramide for Treatment of Migraine.

BACKGROUND: Greater occipital nerve blocks (GONB) are used increasingly to treat acute migraine. OBJECTIVE: We conducted a randomized controlled trial to determine whether GONB was as effective as intravenous metoclopramide for migraine. METHODS: This was a double-dummy, double-blind, parallel-arm, non-inferiority study conducted in 2 emergency departments (EDs). Patients with migraine of moderate or severe intensity were randomized to receive bilateral GONB with each side administered 3 mL of bupivacaine 0.5% or metoclopramide 10 mg IV, the putative standard of care. The primary outcome was improvement in pain on a 0-10 scale between time 0 and 1 hour later. To reject the null hypothesis that metoclopramide would be more efficacious in relieving pain, we required that the lower limit of the 95% CI for the difference in pain improvement between those randomized to GONB vs those randomized to metoclopramide be >-1.3, a validated minimum clinically important difference. Secondary outcomes included sustained headache relief, defined as achieving and maintaining for 48 hours a headache level of mild or none without the use of additional analgesic medication, and the use of rescue medication in the ED. RESULTS: Over a 2.5-year study period, 1358 patients were screened for participation and 99 were randomized, 51 to GONB and 48 to metoclopramide. All of these patients were included in the primary analysis. Patients who received the GONB reported mean improvement of 5.0 (95% CI: 4.1, 5.8) while those who received metoclopramide reported a larger mean improvement of 6.1 (95% CI: 5.2, 6.9). The 95% CI for the between group difference of -1.1 was -2.3, 0.1. Sustained headache relief was reported by 11/51 (22%) GONB and 18/47 (38%) metoclopramide patients (95% CI for rounded difference of 17%: -1, 35%). Of the 51 GONB patients, 17 (33%) required rescue medication in the ED vs 8/48 (17%) metoclopramide patients (95% CI for rounded difference of 17%: 0, 33%). An adverse event was reported by 16/51 (31%) GONB patients and 18/48 (38%) metoclopramide patients (95% CI for (rounded) difference of 6%: -13, 25%). CONCLUSION: GONB with bupivacaine was not as efficacious as IV metoclopramide for the first-line treatment of migraine in the ED.

Opioid Use During the Six Months After an Emergency Department Visit for Acute Pain: A Prospective Cohort Study.

STUDY OBJECTIVE: Despite the frequent use of opioids to treat acute pain, the long-term risks and analgesic benefits of an opioid prescription for an individual emergency department (ED) patient with acute pain are still poorly understood and inadequately quantified. Our objective was to determine the frequency of recurrent or persistent opioid use during the 6 months after the ED visit METHODS: This was a prospective, observational cohort study of opioid-naive patients presenting to 2 EDs for acute pain who were prescribed an opioid at discharge. Patients were followed by telephone 6 months after the ED visit. Additionally, we reviewed the statewide prescription monitoring program database. Outcomes included frequency of recurrent and persistent opioid use and frequency of persistent moderate or severe pain 6 months after the ED visit. Persistent opioid use was defined as filling greater than or equal to 6 prescriptions during the 6-month study period. RESULTS: During 9 months beginning in November 2017, 733 patients were approached for participation. Four hundred eighty-four met inclusion criteria and consented to participate. Four hundred ten patients (85%) provided 6-month telephone data. The prescription monitoring database was reviewed for all 484 patients (100%). Most patients (317/484, 66%; 95% confidence interval 61% to 70%) filled only the initial prescription they received in the ED. One in 5 patients (102/484, 21%; 95% confidence interval 18% to 25%) filled at least 2 prescriptions within the 6-month period. Five patients (1%; 95% confidence interval 0% to 2%) met criteria for persistent opioid use. Of these 5 patients, all but 1 reported moderate or severe pain in the affected body part 6 months later. CONCLUSION: Although 1 in 5 opioid-naive ED patients who received an opioid prescription for acute pain on ED discharge filled at least 2 opioid prescriptions in 6 months, only 1% had persistent opioid use. These patients with persistent opioid use were likely to report moderate or severe pain 6 months after the ED visit.

Predicting the Transition to Chronic Pain 6 Months After an Emergency Department Visit for Acute Pain: A Prospective Cohort Study.

BACKGROUND: Acute pain can transition to chronic pain, a potentially debilitating illness. OBJECTIVE: We determined how often acute pain transitions to chronic pain among patients in the emergency department (ED) and whether persistent pain 1 week after the ED visit was associated with chronic pain. METHODS: An observational cohort study conducted in two EDs. We included adults with acute pain (≤10 days) if an oral opioid was prescribed. Exclusion criteria were recent opioid use and use of any analgesics regularly prior to onset of the pain. Research associates interviewed patients during the ED visit and 1 week and 6 months later. The primary outcome, chronic pain, was defined as pain on > 50% of days since ED discharge. We constructed logistic regression models to evaluate the association between persistent pain 1 week after an ED visit and chronic pain, while adjusting for demographic and treatment variables. RESULTS: During a 9-month period, we approached 733 patients for participation and enrolled 484; 450 of 484 (93%) provided 1-week outcomes data and 410 of 484 (85%) provided 6-month outcomes data. One week after the ED visit, 348 of 453 (77%; 95% confidence interval [CI] 73-80%) patients reported pain in the affected area. New-onset chronic pain at 6 months was reported by 110 of 408 (27%; 95% CI 23-31%) patients. Presence of pain 1 week after ED visit was associated with chronic pain (odds ratio 3.6; 95% CI 1.6-8.5). CONCLUSIONS: About one-quarter of ED patients with acute pain transition to chronic pain within 6 months. Persistence of pain 1 week after the ED visit can identify patients at risk of transition.

A Randomized Trial of a Long-Acting Depot Corticosteroid Versus Dexamethasone to Prevent Headache Recurrence Among Patients With Acute Migraine Who Are Discharged From an Emergency Department.

STUDY OBJECTIVE: Migraine patients continue to report headache during the days and weeks after emergency department (ED) discharge. Dexamethasone is an evidence-based treatment of acute migraine that decreases the frequency of moderate or severe headache within 72 hours of ED discharge. We hypothesize that intramuscular methylprednisolone acetate, a long-acting steroid that remains biologically active for 14 days, will decrease the number of days with headache during the week after ED discharge by at least 1 day compared with intramuscular dexamethasone. METHODS: We conducted a randomized, blinded clinical trial comparing intravenous metoclopramide at 10 mg+intramuscular dexamethasone at 10 mg with intravenous metoclopramide at 10 mg+intramuscular methylprednisolone acetate at a dose of 160 mg for patients presenting to 2 different EDs with moderate or severe migraine. Outcomes were assessed by telephone with a standardized instrument. The primary outcome was number of days with headache during the week after ED discharge. Secondary outcomes were complete freedom from headache, without the necessity of additional headache medication for the entire week after ED discharge, and medication preference, as determined by asking the patient whether he or she would want to receive the same medication again. RESULTS: One hundred nine patients received dexamethasone and 111 received methylprednisolone acetate. We obtained primary outcome data from 101 dexamethasone patients and 106 methylprednisolone acetate patients. Dexamethasone patients reported 3.0 headache days and methylprednisolone acetate 3.3 headache days (95% confidence interval for rounded mean difference of 0.4 days: -0.4 to 1.1). Of 107 dexamethasone patients with analyzable data, 10 (9%) reported complete freedom from headache at 1 week versus 6 of 110 (5%) methylprednisolone acetate patients (95% confidence interval for difference of 4%: -3% to 11%). In the dexamethasone group, 76 of 101 (75%) patients would want the same medication again versus 75 of 106 (71%) of methylprednisolone acetate patients (95% confidence interval for difference of 4%: -8% to 17%). Other than injection site reactions, which were more common in the methylprednisolone acetate group, there were no substantial differences in frequency of adverse events. CONCLUSION: Methylprednisolone acetate does not decrease the frequency of post-ED discharge headache days compared with dexamethasone. Most migraine patients are likely to continue to experience headache during the week after ED discharge.

Randomized Trial of Intravenous Lidocaine Versus Hydromorphone for Acute Abdominal Pain in the Emergency Department.

STUDY OBJECTIVE: We compare the efficacy and safety of intravenous lidocaine with that of hydromorphone for the treatment of acute abdominal pain in the emergency department (ED). METHODS: This was a randomized, double-blind, clinical trial conducted in 2 EDs in the Bronx, NY. Adults weighing 60 to 120 kg were randomized to receive 120 mg of intravenous lidocaine or 1 mg of intravenous hydromorphone. Thirty minutes after administration of the first dose of the study drug, participants were asked whether they needed a second dose of the investigational medication to which they were randomized. Patients were also stratified according to clinical suspicion of nephrolithiasis. The primary outcome was improvement in pain scores of 0 to 10 between baseline and 90 minutes. An important secondary outcome was need for "off-protocol" parenteral analgesics, including opioids and nonsteroidal anti-inflammatory drugs. RESULTS: We enrolled 154 patients, of whom 77 received lidocaine and 77 received hydromorphone. By 90 minutes, patients randomized to lidocaine improved by a mean of 3.8 points on the 0-to-10 scale, whereas those randomized to hydromorphone improved by a mean of 5.0 points (mean difference 1.2; 95% confidence interval 0.3 to 2.2). Need for off-protocol "rescue" analgesics occurred for 39 of 77 lidocaine patients (51%) and 20 of 77 hydromorphone patients (26%) (difference 25%; 95% confidence interval 10% to 40%). Adverse events were comparable between groups. Among the subset of 22 patients with nephrolithiasis, lidocaine patients reported a mean improvement of 3.4 points on the pain scale, whereas hydromorphone patients reported a mean improvement of 6.4 points (mean difference 3.0; 95% confidence interval 0.5 to 5.5). CONCLUSION: Intravenous hydromorphone was superior to intravenous lidocaine both for general abdominal pain and a subset of patients with nephrolithiasis. A majority of patients randomly allocated to lidocaine required additional analgesics.

A Randomized, Placebo-Controlled Trial of Ibuprofen Plus Metaxalone, Tizanidine, or Baclofen for Acute Low Back Pain.

STUDY OBJECTIVE: Patients with low back pain are often treated with nonsteroidal anti-inflammatory drugs and skeletal muscle relaxants. We compare functional outcomes and pain among patients with acute low back pain who were randomized to a 1-week course of ibuprofen plus placebo versus ibuprofen plus 1 of 3 skeletal muscle relaxants: baclofen, metaxalone, and tizanidine. METHODS: This was a randomized, double-blind, parallel-group, 4-arm study conducted in 2 urban emergency departments (EDs). Patients with nonradicular low back pain for less than or equal to 2 weeks were eligible if they had a score greater than 5 on the Roland-Morris Disability Questionnaire, a 24-item inventory of functional impairment caused by low back pain. All participants received 21 tablets of ibuprofen 600 mg, to be taken 3 times a day as needed. Additionally, they were randomized to baclofen 10 mg, metaxalone 400 mg, tizanidine 2 mg, or placebo. Participants were instructed to take 1 or 2 of these capsules 3 times a day as needed. All participants received a 10-minute educational session. The primary outcome was improvement on the Roland-Morris Disability Questionnaire between ED discharge and 1week later. Secondary outcomes included pain intensity 1 week after ED discharge (severe, moderate, mild, or none). RESULTS: Three hundred twenty patients were randomized. One week later, the mean Roland-Morris Disability Questionnaire score of patients randomized to placebo improved by 11.1 points (95% confidence interval [CI] 9.0 to 13.3), baclofen by 10.6 points (95% CI 8.6 to 12.7), metaxalone by 10.1 points (95% CI 8.0 to 12.3), and tizanidine by 11.2 points (95% CI 9.2 to 13.2). At 1-week follow-up, 30% of placebo patients (95% CI 21% to 41%) reported moderate to severe low back pain versus 33% of baclofen patients (95% CI 24% to 44%), 37% of metaxalone patients (95% CI 27% to 48%), and 33% of tizanidine patients (95% CI 23% to 44%). CONCLUSION: Adding baclofen, metaxalone, or tizanidine to ibuprofen does not appear to improve functioning or pain any more than placebo plus ibuprofen by 1 week after an ED visit for acute low back pain.

Randomized Controlled Trial of Intravenous Acetaminophen Versus Intravenous Hydromorphone for the Treatment of Acute Pain in the Emergency Department.

STUDY OBJECTIVE: As clinicians look to nonnarcotic analgesics in the emergency department (ED), it is essential to understand the effectiveness and adverse effects of nonopioid medications in comparison with existing opioid treatments. Studies of intravenous acetaminophen for acute pain in the ED demonstrate mixed results and suffer from small sample sizes and methodological limitations. This study compares intravenous hydromorphone with intravenous acetaminophen in adult ED patients presenting with acute pain. METHODS: This was a prospective, randomized, clinical trial comparing 1 g intravenous acetaminophen with 1 mg intravenous hydromorphone for treatment of adults with severe, acute pain in the ED. The primary outcome was between-group difference in change in numeric rating scale from baseline to 60 minutes postadministration of study medication. Secondary outcomes included the difference in proportion of patients in each group who declined additional analgesia at 60 minutes, received additional medication before 60 minutes, and developed nausea, vomiting, or pruritus. RESULTS: Of 220 subjects randomized, 103 patients in each arm had sufficient data for analysis. At 60 minutes, the mean decrease in numeric rating scale pain score was 5.3 in the hydromorphone arm and 3.3 in the acetaminophen arm, a difference of 2.0 (95% confidence interval [CI] 1.2 to 2.7) favoring hydromorphone. A greater proportion of patients in the hydromorphone arm also declined additional analgesia at 60 minutes (65% versus 44%; difference 21%; (95% CI 8% to 35%). There was no difference in the proportion of patients receiving rescue analgesia before 60 minutes. Significantly more subjects in the hydromorphone group developed nausea (19% versus 3%; difference 16%; 95% CI 4% to 28%) and vomiting (14% versus 3%; difference 11%; 95% CI 0% to 23%). CONCLUSION: Although both 1 mg intravenous hydromorphone and 1 g intravenous acetaminophen provided clinically meaningful reductions in pain scores, treatment with hydromorphone provided both clinically and statistically greater analgesia than acetaminophen, at the cost of a higher incidence of nausea and vomiting.

A Randomized, Double-Blind, Placebo-Controlled Trial of Naproxen With or Without Orphenadrine or Methocarbamol for Acute Low Back Pain.

STUDY OBJECTIVE: In US emergency departments (EDs), patients with low back pain are often treated with nonsteroidal anti-inflammatory drugs and muscle relaxants. We compare functional outcomes among patients randomized to a 1-week course of naproxen+placebo versus naproxen+orphenadrine or naproxen+methocarbamol. METHODS: This was a randomized, double-blind, comparative effectiveness trial conducted in 2 urban EDs. Patients presenting with acute, nontraumatic, nonradicular low back pain were enrolled. The primary outcome was improvement on the Roland-Morris Disability Questionnaire (RMDQ) between ED discharge and 1 week later. All patients were given 14 tablets of naproxen 500 mg, to be used twice a day, as needed for low back pain. Additionally, patients were randomized to receive a 1-week supply of orphenadrine 100 mg, to be used twice a day as needed, methocarbamol 750 mg, to be used as 1 or 2 tablets 3 times per day as needed, or placebo. All patients received a standardized 10-minute low back pain educational session before discharge. RESULTS: Two hundred forty patients were randomized. Baseline demographic characteristics were comparable. The mean RMDQ score of patients randomized to naproxen+placebo improved by 10.9 points (95% confidence interval [CI] 8.9 to 12.9). The mean RMDQ score of patients randomized to naproxen+orphenadrine improved by 9.4 points (95% CI 7.4 to 11.5). The mean RMDQ score of patients randomized to naproxen+methocarbamol improved by 8.1 points (95% CI 6.1 to 10.1). None of the between-group differences surpassed our threshold for clinical significance. Adverse events were reported by 17% (95% CI 10% to 28%) of placebo patients, 9% (95% CI 4% to 19%) of orphenadrine patients, and 19% (95% CI 11% to 29%) of methocarbamol patients. CONCLUSION: Among ED patients with acute, nontraumatic, nonradicular low back pain, combining naproxen with either orphenadrine or methocarbamol did not improve functional outcomes compared with naproxen+placebo.

Helpful Only When Elevated: Initial Serum Lactate in Stable Emergency Department Patients with Sepsis Is Specific, but Not Sensitive for Future Deterioration.

BACKGROUND: Early emergency department (ED) identification of septic patients at risk of deterioration is critical. Lactate is associated with 28-day mortality in admitted patients, but little evidence exists on its use in predicting short-term deterioration. OBJECTIVE: Our aim was to determine the role of initial serum lactate for prediction of short-term deterioration in stable ED patients with suspected sepsis. METHODS: We conducted a prospective cohort study of adult ED sepsis patients. Venous lactate was obtained within 2 h of ED arrival. Main outcome was subsequent deterioration (defined as any of the following: death, intensive care admission > 24 h, intubation, vasoactive medications for > 1 h, or noninvasive positive pressure ventilation for > 1 h) within 72 h. Patients meeting any endpoint within 1 h of arrival were excluded. RESULTS: Nine hundred and eighty-five patients were enrolled, of whom 84 (8.5%) met the primary outcome of deterioration. Initial lactate ≥ 4.0 mmol/L had a specificity of 97% (95% confidence interval [CI] 94-100%), but a sensitivity of 27% (95% CI 18-37%) for predicting deterioration, with positive and negative likelihood ratios of 10.7 (95% CI 6.3-18.3) and 0.8 (95% CI 0.7-0.9), respectively. A lower threshold of lactate (≥2.0 mmol/L) had a sensitivity of 67% (95% CI 55-76%) and specificity of 66% (95% CI 63-69%), with corresponding positive and negative likelihood ratios of 2.0 (95% CI 1.7-2.3) and 0.5 (95% CI 0.4-0.7). CONCLUSIONS: High ED lactate is predictive of subsequent deterioration from sepsis within 72 h, and may be useful in determining disposition, but low lactate is not effective in screening stable patients at risk of deterioration.

Use of the low-frequency/high-frequency ratio of heart rate variability to predict short-term deterioration in emergency department patients with sepsis.

OBJECTIVE: To examine the ability of the low-frequency/high-frequency (LF/HF) ratio of heart rate variability (HRV) analysis to identify patients with sepsis at risk of early deterioration. METHODS: This is a prospective observational cohort study of patients with sepsis presenting to the Montefiore Medical Center ED from December 2014 through September 2015. On presentation, a single ECG Holter recording was obtained and analysed to obtain the LF/HF ratio of HRV. Initial Sequential Organ Failure Assessment (SOFA) scores were computed. Patients were followed for 72 hours to identify those with early deterioration. RESULTS: 466 patients presenting to the ED with sepsis were analysed. Thirty-two (7%) reached at least one endpoint within 72 hours. An LF/HF ratio <1 had a sensitivity and specificity of 34% (95% CI (19% to 53%)) and 82% (95% CI (78% to 85%)), respectively, with positive and negative likelihood ratios of 1.9 (95% CI (1.1 to 3.2)) and 0.8 (95% CI (0.6 to 1.0)). An initial SOFA score ≥3 had a sensitivity and specificity of 38% (95% CI (22% to 56%)) and 92% (95% CI (89% to 95%)), with positive and negative likelihood ratios of 4.9 (95% CI (2.8 to 8.6)) and 0.7 (95% CI (0.5 to 0.9)). The composite measure of HRV+SOFA had improved sensitivity (56%, 95% CI (38% to 73%)) but at the expense of specificity (77%, 95% CI (72% to 80%)), with positive and negative likelihood ratios of 2.4 (95% CI (1.7 to 3.4)) and 0.6 (95% CI (0.4 to 0.9)). Receiver operating characteristic analysis did not identify a superior alternate threshold for the LF/HF ratio. Kaplan-Meier survival functions differed significantly (p=0.02) between low (<1) and high (≥1) LF/HF groups. CONCLUSIONS: While we found a statistically significant relationship between HRV, SOFA and HRV+SOFA, and early deterioration, none reliably functioned as a clinical predictive tool. More complex multivariable models will likely be required to construct models with clinical utility.

Diazepam Is No Better Than Placebo When Added to Naproxen for Acute Low Back Pain.

STUDY OBJECTIVE: Low back pain causes more than 2.5 million visits to US emergency departments (EDs) annually. Low back pain patients are often treated with nonsteroidal anti-inflammatory drugs and benzodiazepines. The former is an evidence-based intervention, whereas the efficacy of the latter has not been established. We compare pain and functional outcomes 1 week and 3 months after ED discharge among patients randomized to a 1-week course of naproxen+diazepam versus naproxen+placebo. METHODS: This was a randomized, double-blind, comparative efficacy clinical trial conducted in an urban health care system. Patients presenting with acute, nontraumatic, nonradicular low back pain of no more than a duration of 2 weeks were eligible for enrollment immediately before discharge from an ED if they had a score greater than 5 on the Roland-Morris Disability Questionnaire, a validated 24-item inventory of functional impairment caused by low back pain. Higher scores on the questionnaire indicate greater functional disability. The primary outcome in the trial was improvement in the score between ED discharge and 1 week later. Secondary outcomes included pain intensity 1 week and 3 months after ED discharge, as measured on a 4-point descriptive scale (severe, moderate, mild, and none). All patients were given 20 tablets of naproxen 500 mg, to be taken twice a day as needed for low back pain. Additionally, patients were randomized to receive either 28 tablets of diazepam 5 mg or identical placebo, to be received as 1 or 2 tablets every 12 hours as needed for low back pain. All patients received a standardized 10-minute low back pain educational session before discharge. Using a between-group mean difference of 5 Roland-Morris Disability Questionnaire points, a previously validated threshold for clinical significance, we calculated the need for at least 100 patients with primary outcome data. RESULTS: Enrollment began in June 2015 and continued for 9 months. Five hundred forty-five patients were screened for eligibility. One hundred fourteen patients met selection criteria and were randomized. Baseline demographic characteristics were not substantially different between the 2 groups. One hundred twelve patients (98%) provided 1-week outcome data. The mean Roland-Morris Disability Questionnaire score of patients randomized to naproxen+diazepam improved by 11 (95% confidence interval [CI] 9 to 13), as did the mean score of patients randomized to naproxen+placebo (11; 95% CI 8 to 13). At 1-week follow-up, 18 of 57 diazepam patients (32%; 95% CI 21% to 45%) reported moderate or severe low back pain versus 12 of 55 placebo patients (22%; 95% CI 13% to 35%). At 3-month follow-up, 6 of 50 diazepam patients (12%; 95% CI 5% to 24%) reported moderate or severe low back pain versus 5 of 53 placebo patients (9%; 95% CI 4% to 21%). Adverse events were reported by 12 of 57 diazepam patients (21%; 95% CI 12% to 33%) and 8 of 55 placebo patients (15%; 95% CI 7% to 26%). CONCLUSION: Among ED patients with acute, nontraumatic, nonradicular low back pain, naproxen+diazepam did not improve functional outcomes or pain compared with naproxen+placebo 1 week and 3 months after ED discharge.

Comparative Effectiveness of Patient-Controlled Analgesia for Treating Acute Pain in the Emergency Department.

STUDY OBJECTIVE: We assess the effectiveness of patient-controlled analgesia in the emergency department (ED). We hypothesized that decline in pain intensity from 30 to 120 minutes after initial intravenous opioid administration is greater in patients receiving morphine by patient-controlled analgesia compared with usual care and would differ by a clinically significant amount. METHOD: This was a pragmatic randomized controlled trial of patient-controlled analgesia and usual care (opioid and dose at physician's discretion) in 4 EDs. Entry criteria included age 18 to 65 years and acute pain requiring intravenous opioids. The primary outcome was decline in numeric rating scale pain score 30 to 120 minutes postbaseline. Secondary outcomes included satisfaction, time to analgesia, adverse events, and patient-controlled analgesia pump-related problems. We used a mixed-effects linear model to compare rate of decline in pain (slope) between groups. A clinically significant difference between groups was defined as a difference in slopes equivalent to 1.3 numeric rating scale units. RESULTS: Six hundred thirty-six patients were enrolled. The rate of decline in pain from 30 to 120 minutes was greater for patients receiving patient-controlled analgesia than usual care (difference=1.0 numeric rating scale unit; 95% confidence interval [CI] 0.6 to 1.5; P<.001) but did not reach the threshold for clinical significance. More patients receiving patient-controlled analgesia were satisfied with pain management (difference=9.3%; 95% CI 3.3% to 15.1%). Median time to initial analgesia was 15 minutes longer for patient-controlled analgesia than usual care (95% CI 11.4 to 18.6 minutes). There were 7 adverse events in the patient-controlled analgesia group and 1 in the usual care group (difference=2.0%; 95% CI 0.04% to 3.9%), and 11 pump-programming errors. CONCLUSION: The findings of this study do not favor patient-controlled analgesia over usual ED care for acute pain management.

Predicting three-month functional outcomes after an ED visit for acute low back pain.

BACKGROUND: Nearly 30% of patients who present to an ED with acute, new onset, low back pain (LBP) report LBP-related functional impairment three months later. These patients are at risk of chronic LBP, a highly debilitating condition. It has been reported previously that functional impairment, depression, and psychosomatic symptomatology at the index visit are associated with poor LBP outcomes. We wished to replicate those findings in a cohort of ED patients, and also to determine if clinical features present at one week follow-up could predict three-month outcomes in individual patients. METHODS: This was a planned analysis of data from a randomized comparative effectiveness study of three analgesic combinations conducted in one ED. Patients were followed by telephone one week and three months post-ED visit. The primary outcome was a three-month Roland-Morris Disability Questionnaire (RMDQ) score >0, indicating the presence of LBP-related functional impairment. At the index visit, we measured functional impairment (using the RMDQ), depressive symptomatology (using the Patient Health Questionnaire depression module), and psychosomatic features (using the 5-item Cassandra scale). At the one-week follow-up, we ascertained the presence or absence of LBP. We built a logistic regression model in which all the predictors were entered and retained in the model, in addition to socio-demographic variables and dummy variables controlling for investigational medication. Results are reported as adjusted odds ratios (adjOR) with 95% CI. To determine if statistically significant associations could be used to predict three-month outcomes in individual patients, we then calculated positive and negative likelihood ratios [LR(+) and LR(-)] with 95% CI for those independent variables associated with the primary outcome. RESULTS: Of 295 patients who completed the study, 14 (5%) were depressed and 18 (6%) reported psychosomatic symptoms. The median index visit RMDQ score was 19 (IQR: 17, 21) indicating substantial functional impairment. One week after the ED visit, 193 (65%) patients reported presence of LBP. 294 patients provided a three-month RMDQ score, 88 of whom (30%, 95% CI: 25, 35%) reported a score >0. Neither depression (adjOR 0.7 [95% CI 0.2, 3.1]), psychosomatic symptomatology (adjOR 0.5 [95% CI 0.1, 2.0]), nor index visit functional impairment (adjOR 1.0 [95% CI 1.0, 1.1]) were associated with three-month outcome. Pain at one week was strongly and independently associated with the three-month outcome when examined at the group level (adjOR 4.0 [95% CI 2.1, 7.7]). However, likelihood ratios for pain or its absence at one-week were insufficiently robust to be clinically useful in predicting three-month outcomes in individual patients (LR+: 1.4 [95% CI: 1.3, 1.7]; LR-: 0.4 [95% CI: 0.2, 0.6]). CONCLUSIONS: In spite of a strong association at the group level between presence of LBP at one week and functional impairment at three months, when used to predict outcomes in individual patients, presence of pain failed to discriminate with clinically meaningful utility between acute LBP patients destined to have a favorable versus unfavorable three-month outcome.

Efficacy of an Acute Pain Titration Protocol Driven by Patient Response to a Simple Query: Do You Want More Pain Medication?

STUDY OBJECTIVE: We assess the efficacy of a simple pain titration protocol of 1-mg increments of intravenous hydromorphone, given at fixed intervals, driven solely by patient response to a yes/no question. METHODS: This was a prospective interventional cohort study of nonelderly adults with acute severe pain defined as requiring intravenous opioids in the judgment of the attending emergency physician. All patients received 1 mg intravenous hydromorphone and 30 minutes later were asked, "Do you want more pain medication?" Patients responding yes received an additional 1 mg of intravenous hydromorphone and were asked the same question 30 minutes after receiving it. Those responding no did not receive additional opioid and were asked the question again 30 minutes later. Each patient was queried 4 times. The primary endpoint was the proportion of patients achieving satisfactory pain control, defined as declining additional pain medication on 1 or more occasions. RESULTS: Of 215 patients enrolled, there were 8 protocol violations, leaving 207 patients with analyzable data; 205 of 207 patients (99%; 95% confidence interval 97% to 100%) achieved satisfactory analgesia at 1 or more points during the study. Nine patients desaturated below 95% on room air, 2 had respiratory rates less than 10 breaths/min, and 2 had pulse rates less than 50 beats/min. No adverse events were associated with amount of hydromorphone received. CONCLUSION: A pain protocol, based on titration of 1 mg intravenous hydromorphone, driven solely by patient response to a simple standardized question repeated at intervals, resulted in achievement of satisfactory analgesia on at least 1 occasion in 99% of patients.

Diphenhydramine as Adjuvant Therapy for Acute Migraine: An Emergency Department-Based Randomized Clinical Trial.

STUDY OBJECTIVE: More than 1 million patients present to US emergency departments (EDs) annually seeking care for acute migraine. Parenteral antihistamines have long been used in combination with antidopaminergics such as metoclopramide to treat acute migraine in the ED. High-quality data supporting this practice do not exist. We determine whether administration of diphenhydramine 50 mg intravenously+metoclopramide 10 mg intravenously results in greater rates of sustained headache relief than placebo+metoclopramide 10 mg intravenously. METHODS: This was a randomized, double-blind, clinical trial comparing 2 active treatments for acute migraine in an ED. Eligible patients were adults younger than 65 years presenting with an acute moderate or severe headache meeting International Classification of Headache Disorders-2 migraine criteria. Patients were stratified according to presence or absence of allergic symptoms. The primary outcome was sustained headache relief, defined as achieving a headache level of mild or none within 2 hours of medication administration and maintaining this level of relief without use of any additional headache medication for 48 hours. Secondary efficacy outcomes included mean improvement on a 0 to 10 verbal scale between baseline and 1 hour, the frequency with which subjects indicated they would want the same medication the next time they present to the ED with migraine, and the ED throughput time. Sample size calculation using a 2-sided α of .05, a ß of .20, and a 15% difference between study arms determined the need for 374 patients. An interim analysis was conducted when data were available for 200 subjects. RESULTS: Four hundred twenty patients were approached for participation. Two hundred eight eligible patients consented to participate and were randomized. At the planned interim analysis, the data and safety monitoring board recommended that the study be halted for futility. Baseline characteristics were comparable between the groups. Fourteen percent (29/208) of the sample reported allergic symptoms. Of patients randomized to diphenhydramine, 40% (40/100) reported sustained relief at 48 hours, as did 37% (38/103) of patients randomized to placebo (95% confidence interval [CI] for difference of 3%: -10% to 16%). One hour after medication administration, patients randomized to diphenhydramine improved by a mean of 5.1 on the 0 to 10 scale versus 4.8 for those randomized to placebo (95% CI for difference of 0.3: -0.6 to 1.1). Eighty-five percent (84/99) of the patients in the diphenhydramine arm reported they would want the same medication combination during a subsequent ED visit, as did 76% (77/102) of those who received placebo (95% CI for difference of 9%: -2% to 20%). Median ED length of stay was 122 minutes (interquartile range 84 to 180 minutes) in the diphenhydramine group and 139 minutes (interquartile range 90 to 235 minutes) in the placebo arm. Rates of adverse effects, including akathisia, were comparable between the groups. CONCLUSION: Intravenous diphenhydramine, when administered as adjuvant therapy with metoclopramide, does not improve migraine outcomes.

Current management of migraine in US emergency departments: an analysis of the National Hospital Ambulatory Medical Care Survey.

BACKGROUND: Published data from 1998 revealed that most patients treated for migraine in an emergency department received opioids. Over the intervening years, a large body of evidence has emerged demonstrating the efficacy and safety of non-opioid alternatives. Expert opinion during these years has cautioned against use of opioids for migraine. Our objectives were to compare current frequency of use of various medications for acute migraine in US emergency departments with use of these same medications in 1998 and to identify factors independently associated with opioid use. METHODS: We analyzed National Hospital Ambulatory Medical Care Survey data from 2010, the most current dataset available. The National Hospital Ambulatory Medical Care Survey is a public dataset collected and distributed by the Centers for Disease Control and Prevention. It is a multi-stage probability sample from randomly selected emergency departments across the country, designed to be representative of all US emergency department visits. We included in our analysis all patients with the ICD9 emergency department discharge diagnosis of migraine. We tabulated frequency of use of specific medications in 2010 and compared these results with the 1998 data. Using a logistic regression model, into which all of the following variables were entered, we explored the independent association between any opioid use in 2010 and sex, age, race/ethnicity, geographic region, type of hospital, triage pain score and history of emergency department use within the previous 12 months. RESULTS: In 2010, there were 1.2 (95% confidence interval 0.9, 1.4) million migraine visits to US emergency departments. Including opioid-containing oral analgesic combinations, opioids were administered in 59% of visits (95% confidence interval 51, 67). The most commonly used parenteral agent, hydromorphone, was used in 25% (95% confidence interval 19, 33) of visits in 2010 versus less than 1% (95% confidence interval 0, 3) in 1998. Conversely, use of meperidine had decreased markedly over the same timeframe. In 2010, it was used in just 7% (95% confidence interval 4, 12) of visits compared to 37% (95% confidence interval 29, 45) in 1998. Metoclopramide, the most commonly used anti-dopaminergic, was administered in 17% (95% confidence interval 12, 23) of visits in 2010 and 3% (95% confidence interval 1, 6) of visits in 1998. Use of any triptan was relatively uncommon in 2010 (7% (95% confidence interval 4, 11) of visits) and in 1998 (10% (95% confidence interval 6, 15) of visits). Of the predictor variables listed above, only emergency department use within the previous 12 months was associated with opioid administration (adjusted odds ratio: 2.87 (95% confidence interval 1.03, 7.97)). CONCLUSIONS: In spite of recommendations to the contrary, opioids are still used in more than half of all emergency department visits for migraine. Though use of meperidine has decreased markedly between 1998 and 2010, it has largely been replaced by hydromorphone. Opioid use in migraine visits is independently associated with prior visits to the same emergency department in the previous 12 months.

Age But Not Sex Is Associated With Efficacy and Adverse Events Following Administration of Intravenous Migraine Medication: An Analysis of a Clinical Trial Database.

BACKGROUND: Migraine prevalence is associated with both sex and age. Differences in efficacy of parenteral migraine medication administration based on the sex and age of the patient have not been explored in the published literature. OBJECTIVE: The objective was to determine whether sex and age are associated with short-term headache relief, sustained headache freedom, or adverse medication effects in data collected during 3 emergency department (ED)-based acute migraine comparative efficacy trials. METHODS: Data were combined from 3 studies in which patients who presented to an ED with acute migraine were randomized to one of the following intravenous medication regimens: (1) metoclopramide combined with diphenhydramine; (2) metoclopramide combined with diphenhydramine and dexamethasone; (3) metoclopramide alone; (4) ketorolac; or (5) valproate. In each of these studies, (1) short-term efficacy (patient description of the headache as "mild" or "none" 1 hour after medication administration); (2) sustained efficacy (patient description of the headache as "none" within 2 hours of medication administration and no headache recurrence for 24 hours post ED discharge); and (3) the frequency of any adverse medication effects within 24 hours of medication administration was determined. For each of the medication regimens studied, efficacy and adverse event rates were compared between men vs women and the older vs the younger half of patients. Multivariate logistic regression models were constructed in which sex and age were maintained in the model as well as variables representing each of the medication regimens patients received. RESULTS: A total of 884 patients were included in this analysis (140 men and 744 women). The median age was 35 years. After controlling for age and medication received, female sex was not associated with short-term efficacy (OR 0.98 [95% confidence interval (CI): 0.66, 1.46]), sustained efficacy (OR 0.72 [95%CI: 0.45, 1.15]), or adverse events (OR 1.14 [95%CI: 0.77, 1.71]). Age >36 years, however, was associated with short-term efficacy (OR 0.66 [95%CI: 0.49, 0.88]), sustained efficacy (OR 0.50 [95%CI: 0.34, 0.73]), and adverse events (OR 1.36 [95%CI: 1.02, 1.82]). CONCLUSION: Sex was not associated with response to parenteral acute migraine medication. Age was associated with both efficacy and adverse events.

Comparative Analgesic Efficacy of Oxycodone/Acetaminophen vs Codeine/Acetaminophen for Short-Term Pain Management Following ED Discharge.

OBJECTIVE: To test the hypothesis that oxycodone/acetaminophen provides analgesia superior to codeine/acetaminophen following emergency department (ED) discharge. DESIGN: Prospective, randomized, double-blind, trial. SETTING: Adult inner city ED. SUBJECTS: ED patients with acute extremity pain who were discharged home. METHODS: Patients randomized to oxycodone/acetaminophen (5 mg/325 mg) or codeine/acetaminophen (30 mg/300 mg). The primary outcome, obtained via telephone one day after ED discharge, was the between-group difference in improvement in numerical rating scale (NRS) pain scores over a 2-hour period following the most recent ingestion of study drug. Secondary outcomes included proportion of patients with >50% pain reduction, side-effect profile, and patient satisfaction. RESULTS: Two hundred and forty patients were enrolled. Mean baseline NRS scores were 7.9 in both groups. Mean decrease over 2 hours was 4.5 NRS units in the oxycodone/acetaminophen group vs 4.2 NRS units in the codeine/acetaminophen group, for a clinically and statistically nonsignificant difference of 0.2 NRS units (95% CI -0.4-0.9 NRS units). Similarly, 66% vs 61% achieved >50% pain relief for a nonsignificant difference of 5% (95% CI -8% to 17%). Side-effect profile and patient satisfaction were similar. CONCLUSION: Our hypothesis that oxycodone/acetaminophen provides analgesia superior to codeine/acetaminophen was rejected. Although pain within each group was reduced by more than half, the between-group difference was not significant. Pending independent validation, these unexpected findings suggest that codeine/acetaminophen, a Schedule III agent, may be a clinically reasonable outpatient opioid alternative to oxycodone/acetaminophen, a more tightly restricted Schedule II agent thought to be more prone to misuse.